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The controversy over the “Memory of Water”, Med Sci Hypotheses 2017; 4:1-6

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Received: 2016.08.22
Accepted: 2016.11.22
Published: 2017.01.03
3371 27
The Controversy Over the “Memory of Water”
DE George Vithoulkas
Corresponding Author: George Vithoulkas, e-mail: george@vithoulkas.com
Source of support: Self financing
For a very long time, the idea of the “memory of water” tantalized not only the homeopathic community, but
also serious scientists and researchers like Luc Antoine Montagnier, a recipient of the Nobel Prize.
This misconception originated from an experiment conducted by the famous allergologist, Dr. Jacques Benveniste.
He claimed to have shown in an in vitro experiment that highly dilute potencies of bee poison (apis mellifi-
ca), even beyond the Avogadro number, are capable of producing structural changes in living organisms in the
same way that the real poison from the bee can bring these changes about, being the actual degranulation of
basophils. His paper was published in Nature under an obligation to prove his findings in front of a scientific
committee in his own laboratory. Benveniste could not reproduce the results that his team was claiming.
When a similar experiment was repeated by a different group of scientists and filmed by the BBC, it also failed.
While it was obvious that the experiment was proved to be false, the scientific community concluded, by an
extension of logic, that since the experiment was false, therefore homeopathy must also be a false system of
therapy.
Despite the fact that the experiment was repeatedly invalidated, some scientists, especially in the homeopath-
ic community, continued to believe that Benveniste’s findings were true.
In this way, the scientific community remains in confusion as to whether: a) water has memory, or b) homeop-
athy is or is not a valid system of therapy.
Since I have been an eye-witness of these events from their very beginnings, I am giving an account of the real
story for both the homeopathic community and the sceptics.
MeSH Keywords: Basophil Degranulation Test • Homeopathy • Indicator Dilution Techniques
Full-text PDF: http://www.medscihypothesis.com/abstract/index/idArt/901167
Authors’ Contribution:
Study Design A
Data Collection B
Statistical Analysis C
Data Interpretation D
Manuscript Preparation E
Literature Search F
Funds Collection G
Kiev Medical Academy and International Academy of Classical Homeopathy,
Alonissos, Greece
ISSN 2373-3551
© Med Sci Hypotheses, 2017; 4: 1-6
DOI: 10.12659/MSH.901167
1
The Controversy Over the “Memory of
Water”
A long time has elapsed, over 20 years in fact, since the time
of the Benveniste’s experiment, but still, this peculiar story of
the “memory of water” tantalizes the scientific and homeo-
pathic community.
The now deceased Dr Jacques Benveniste [1], a famous French
professor of immunology, claimed to have shown in an ex
-
periment that highly dilute potencies of homeopathic reme-
dies, even beyond the Avogadro number, are capable of pro-
ducing structural changes in living organisms (cell cultures,
in this case [2]).
In other words, he claimed to have definitively shown through
his experiment the effectiveness of the homeopathic high po-
tencies [3].
The Benveniste experiment was proved to be false.
Despite the fact that the experiment was invalidated, some in
the homeopathic community continue, even today, to believe
that his findings were true.
The idea of the “memory of water” tantalizes even serious sci-
entists like Luc Antoine Montagnier [4], a French virologist and
recipient of the Nobel Prize [5].
The Benveniste experiment which, shortly after the release of
its findings, were proved false by a scientific committee sent
by the international scientific journal Nature to his laboratory,
damaged the reputation of homeopathy more than any oth-
er event in homeopathy’s long history. The reason being that
many of the most vicious subsequent attacks on homeopa-
thy have been based on this false experiment, which has been
perpetuated and ridiculed by journalists and sceptics based
on the idea that water has memory [6–22].
Therefore, we encountered a strange situation whereby a true
and effective healing methodology was invalidated by the scep-
tics because of a false experiment!
I believe that, as I was an eye-witness of these events, I should
give an account of the real story for both the homeopathic
community and the sceptics.
Here are the facts
In 1988, Temple University of Philadelphia organized a meet-
ing of scientists on the Bermuda Islands to conduct an open
discussion on issues that pertained to the “borders” of sci-
ence. All the delegates were highly reputed professors; some
were also Nobel Prize laureates. Benveniste was invited to the
meeting, as well as myself.
The theme of that meeting was “Frontiers of Science”. Some
delegates presented new ideas from their research. Benveniste
spoke on his “incredible” findings in relation to micro-dilu-
tions, meaning the high potencies of homeopathy, beyond
the Avogadro number. I was the only delegate who could un-
derstand what he was talking about, so I was the only one
amongst all the delegates who could criticize his findings.
What he claimed in effect was that when you are stung by a
bee, there are certain defense processes activated, one of which
is degranulation of basophils. He then went further to claim
that he discovered through his experiments in his laboratory
that if the same substance (the bee poison) is diluted beyond
Avogadro’s number, where not even one molecule of the poison
exists anymore in the dilution, such a dilution can also cause
structural changes in the organism, similar to the ones caused
by the actual poison; namely, the degranulation of basophils!
It was obvious that Benveniste, not being a homeopath, did
not understand what a high potency of a remedy can or can-
not do. Probably his false concept originated from a misun-
derstanding of the basic laws of homeopathy. Not only was
he not a homeopath, but no-one in his team was a practitio-
ner of homeopathy.
A high potency can never bring about a structural change in
the organism, like the one Benveniste claimed. In homeopa-
thy, we use hundreds of poisonous substances, much more vir-
ulent than the bee sting, and never have we observed struc-
tural damage in a person. If we had such obvious proof of the
action of high potencies, there would be no reason for dis-
cussing it today, because the proof of the action of high po-
tencies would be self-evident.
From his unbelievable statement, there was huge amaze-
ment within the audience! His findings appeared to be really
beyond the frontiers of science. As soon as he completed his
presentation, I objected by saying that “your findings cannot
be true according to the principles of homeopathy…”. As soon
as I voiced my objection, Benveniste reacted with tremendous
anger and indignation. I did not continue the argument, as he
appeared to be deeply hurt.
The problem was that at the end of his talk, Benveniste plead-
ed with all the influential scientists present to exercise their
influence so as to ensure that his paper would be accepted
by Nature.
In the outer circle of observers, there was a professor of med-
icine and an expert in allergology, Zvi Bentwitch, from Hebrew
2
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University, whom I knew from previous discussions on ho-
meopathy. During the break, Prof. Bentwitch approached me
and asked me to explain why I had objected to Benveniste’s
experiment. He also told me that he himself was involved in
this experiment, having been asked to independently confirm
Benveniste’s findings through his own laboratory.
I explained to Prof. Bentwitch that if what Benveniste was say-
ing was true, then all the remedies derived from poisons that
we were using in homeopathy in high potencies could have a
damaging effect causing structural changes in organisms in
the same way all poisons do. He saw immediately the logic
of the argument and confessed to me that he had tried to re-
produce the results in his laboratory but could not see what
Benveniste claimed to have seen under the microscope in his
own laboratory. Prof. Zvi Bentwitch had invited Benveniste’s
technician to come to Israel and show them, under the micro-
scope, the basophilic degranulation, but still they could not see
the claimed effect. After our subsequent talk, which confirmed
his findings, he withdrew from the experiment.
Shortly after this presentation, an article appeared in the
press and on its front page was the news from the Congress
in Bermuda saying that according to Benveniste’s experiment,
“water had memory”! The naming “memory of water” was ac-
tually the conclusion of the journalist, not of Benveniste, and
this nonsense was destined to become later an object for rid-
iculing homeopathy.
In his original paper, Benveniste never mentioned the idea of
the memory of water. In the meantime, those scientists pres-
ent at the Bermuda Congress did finally influence the journal
Nature to publish Benveniste’s paper. Nature agreed to pub-
lish it on the condition that Benveniste would agree to show
afterwards to a group of experts the results of his experiment
under the microscope in his laboratory in Paris.
The expert team consisted of John Maddox, editor of Nature;
Walter Stewart, an expert on science; and James Randi, a pro-
fessional magician and an expert on fraud.
In his laboratory, Benveniste and his team repeated the ex-
periment. When this committee looked under the microscope
in Paris, they couldn’t see any degranulation of basophils as
Benveniste was claiming [23]. The fiasco was publicized aggres-
sively by the media the next day [24]. The British Broadcasting
Company (BBC) Television devoted a three-hour discussion to
this unfortunate affair.
As was expected, this event resulted in a huge scandal amongst
the scientific community of the time. Benveniste lost his po-
sition in the University, lost his laboratory, and, needless to
say, lost his prestige, his financial support, and his reputation.
Despite these facts, many homeopaths and lay people, for some
reason, continued to believe in the “memory of water”. The is-
sue in the media since then became not one of whether high
potencies had a curative effect on the sick, but whether water
has or has not memory. Furthermore, if water did not have
memory, then homeopathy was a false healing methodology!
The Continuation of The Ridicule
As a result of such ongoing beliefs and discussions, a second
team of scientists, after a few years, astonishingly claimed that
Benveniste might have been right after all. They claimed that they
repeated the experiment and, surprisingly, it worked. Professor
Madeleine Ennis [25] of Queen’s University, Belfast, was one of
the writers. This time the matter was taken up directly by the
BBC, which, together with another team of scientists, along with
Randi, took up the challenge and agreed to film what these sci-
entists were claiming and again make it public in a BBC program.
This was a second disaster for homeopathy, as the investigat-
ing committee could not see any degranulation of basophils
and, unfortunately, even greater damage occurred because the
BBC made the results of the investigation known to the world
for a second time in an infamous production of Horizon [26].
The conclusion of this program was that homeopathy is next
to nonsense and that we should forget about homeopathy.
I immediately wrote a letter to the Chief Editor of the program
explaining the situation as I knew it.
Here is the correspondence:
To The Chief Editor of the Horizon Program
Mr Matthew Barrett
Room 4523
BBC, White City
201 Wood Lane
London W12 7TS
UK
Alonissos, Greece, 27-9-2003
Subject: Horizon –Homeopathy- Randi
Dear Mr. Barrett,
As one who has devoted his life to the teaching of Homeopathy, I
watched with great interest the Horizon program on Homeopathy.
In 1988, I had the honour to participate in an international as-
sembly of some of the leading conventional scientists, talking
on “the frontiers of” science, which took place in Bermuda, or-
ganized by Temple University of Philadelphia. One of the par-
ticipants of this meeting was Dr. Benveniste who presented his
3
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research. On this occasion, I did not hesitate to object strongly
to his findings, on the ground that they contradicted the basic
principles of homeopathy. According to these principles, a highly
diluted and potentized substance will have an action opposite
to its action in its undiluted state. Therefore, to use Benveniste’s
model, the highly diluted antigen, would be expected rather to
suppress basophil degranulation, than cause such a degranula-
tion (refer correspondence below: Re: Horizon on Homeopathy,
George Vithoulkas – 2nd posting – 9 Oct 2003, 12: 06).
To give a simpler example, if a substance is taken in big enough
quantity, it is able to create a set of symptoms, but in its high
potency counteracts these very symptoms. So, the symptoms of
a sting by a bee (an allergic reaction that causes degranulation)
will be expected to be reduced by a high potency of the homeo-
pathic remedy Apis Mellifica (coming from a crushed and poten-
tized bee) but could never produce such allergic condition of
degranulation of basophils as Benveniste claimed.
Unfortunately, Benveniste’s research was published in the pres-
tigious scientific magazine Nature, and therefore is still perpet-
uated by some scientists, causing more and more confusion to
this important therapeutic modality.
The regrettable thing in this – excellent in execution – film, was
that all the arguments against homeopathy were based on a
wrong assumption by Benveniste and on dubious research,
while it gave the impression of having been conducted in an ob-
jective and scientifically sound way when in fact it was based on
a wrong assumption and with an inappropriate methodology.
But I could not see how the conclusion was drawn at the end of
the film that ‘homeopathy does not work’ just because one ex-
periment - based on a wrong assumption - failed!
To insist in not accepting a therapeutic system because of lack
of understanding in its underlying theory, instead of appreciat-
ing its therapeutic results, seems to me quite hypocritical on the
part of conventional medicine. Until a few years ago, we did not
even know how aspirin worked, yet it was the most frequently
prescribed drug in conventional medicine.
To give another example I could say that if the scientists who dis-
covered electricity wanted first to know how this phenomenon
was produced before they could use electricity, then most proba-
bly we would still be in darkness. It took hundreds of years to coin
a theory: that it is movement of electrons, and even today we do
not know the nature of any type of energy, let alone electricity.
Homeopathy uses a type of energy unravelled through the pro-
cess of potentization (not through simple dilution as was hint-
ed in the film). The fact is that at this moment we do not have
conclusive evidence of what is the nature of this energy. Full
stop! But we define energy only as ‘that which has the ability
to produce some effect’.
Homeopathy therefore must be accepted or rejected on its ther-
apeutic effects alone.
I do not know who suggested using the Benveniste experiment
as something that would validate or disprove homeopathy. If it
was Mr. Randi himself, I am afraid that he has done a disser-
vice to humanity.
By your film, you have created a perception of homeopathy that
will cause people to not consider a therapeutic method that oth-
erwise would have been found to be very beneficial.
Yours sincerely
Prof. George Vithoulkas
Alternative Nobel Prize 1996
Cc The Chief Editor of Nature
My letter was given to the producer of the Horizon to answer
and here is his response:
Dear Prof. George Vithoulkas,
Thank you for your letter concerning the Horizon program on
Homeopathy. Matthew Barrett asked me to reply as I was the
producer of that program. I’d like to answer a few of the points
you raise in your letter.
The key point we were making about homeopathy is not just
that we don’ t know how it works, but that if it works it means
that scientific understanding is fundamentally wrong in some
important respects. For a high-potency homeopathic medicine to
have a pharmacological effect our basic understanding of matter
would have to be rewritten. Therefore, for homeopathy to work
it is a necessary (but not sufficient) requirement that sub-mo-
lecular dilutions have some effect on biological systems. You are
quite correct that this would not in itself prove homeopathy and
that certain ultra-dilution effects might provide better evidence
for homeopathy than others. However, we decided to give ho-
meopathy the ‘benefit of the doubt’ and allow that any demon-
stration of an effect from a sub-molecular dilution would show
that this scientific principle was wrong and so provide support
for homeopathy (whether directly or indirectly).
We therefore sought advice (in particular from homeopaths)
and were told that the Ennis experiments provided the most
convincing such evidence. Therefore, it was this system that we
used – and sadly were unable to replicate. We were not asking
that anyone explain the mechanism by which sub-molecular di-
lutions have an effect, merely that they demonstrate that sub-
molecular dilutions do have an effect.
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You say that homeopathy must be accepted or rejected on its
therapeutic effects alone – and we showed in the programme
claims of therapeutic effect of both clinical and anecdotal.
However, it is the opinion of the most scientists and many ho-
meopaths that given the conflicting results of controlled trials
that there will never be enough purely therapeutic evidence to
convince science that homeopathy works. Therefore, it is vital
that homeopaths are able to show in a reproducible experimen-
tal system that sub-molecular dilutions can have a biological ef-
fect. It appears that no such system yet exists.
Yours sincerely
Nathan Williams, BBC Horizon
Here is my answer to him
Alonissos-Greece, 5-10-2003
Mr Nathan Williams
Producer of the Horizon Program
Room 4523
BBC, White City
201 Wood Lane
London, W12 7TS
UK
Dear Mr Nathan Williams,
Thank you for your reply.
It is a basic principle in homeopathy that in order to have an ef-
fect with a highly diluted and potentized remedy such a reme-
dy must fit the totality of the symptoms of the patient. It is a
highly individualized therapy.
(What) were the ‘symptoms of the cells’ in the Benveniste exper-
iment in order that the remedy would have shown some effect?
Since this aspect of Homeopathy was not respected in these ex-
periments we cannot say that homeopathy was tested. An “idea”
was tested but not homeopathy.
This was the point I was making in my previous letter.
There is no meaning in this communication to go deeper in to
the fallacies and complications of the Benveniste experiment.
Suffice to say that if the blood cells were coming from an aller-
gic – to the bees – patient, so you would have already in exis-
tence a ‘sensitivity’ between the remedy Apis Mellifica (com-
ing from a crushed bee) and the diseased cells - then you might
have observed some kind of reaction on the cellular level, but
only in this condition and in no other and surely not of the kind
of reaction described by Benveniste.
One has to take into account that homeopathy is the most dif-
ficult -in its application- therapeutic modality existing today.
Its demand is universal, but the practitioners are not educated
properly (since it is not taught in medical schools) and because
of such demand a lot of charlatanism is injected into this ther-
apeutic modality. So, anybody’s reservations are justified to a
certain extend.
I want to conclude this letter by saying that everyone is aware of
the integrity of the BBC – and I am sure you will do something to
balance the damage done so far to homeopathy with this film...
Sincerely yours
George Vithoulkas
After this reply, the matter went to the BBC scientific post-
ing and was followed by various comments from a range of
scientists.
Conclusions
The fact is that Benveniste’s false experiment caused home-
opathy to be attacked viciously by its enemies [27].
The misunderstanding was caused because of a superficial
idea of the reporting journalist to say that water had memory.
Whether water has memory or not is not the issue, what is
important to understand is why a highly potentized remedy
has a biological effect on a sick organism.
It is well known in homeopathy that if you simply dilute a sub-
stance in water to such a degree as to have left no molecule
in the solution, then this solution will have no effect what-
ever on the human organism - whether water has or has not
memory. The effectiveness of the remedies comes ONLY if the
solution is potentized (succussed) in serial potentiations. It is
ONLY the potentization of the water that transforms the con-
stituency of the water so as to attain the biological effect that
the remedy has upon living organisms.
For all those knowledgeable in homeopathic principles, it would
suffice to say that only if a high potency of a remedy fits the
totality of the symptoms of a patient, then in such a case the
remedy will eliminate those symptoms.
That is why in the proving of remedies, material doses were/are
used to cause the toxic effects. High potencies will cause some
subtle functional symptoms and these only in some sensi-
tive people, but never structural changes like the degranula-
tion of basophils.
5
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What I was trying to say in the debates with the BBC and to
the interested scientists is that you cannot condemn a heal-
ing method which is 200 years old that has an impressive re-
cord of cure just because someone had conceived and con-
ducted a false experiment.
Epilogue – The New Experiment
After these events, Mr. Randi, the magician, put up on his web-
site an announcement saying in effect that if anybody could
prove the action of homeopathic high dilutions, they will re-
ceive a prize of one million dollars that was standing in a ded-
icated bank account.
A team of ten Greek medical doctors and I took up this chal-
lenge and agreed on an experiment to prove that high poten-
cies of homeopathic remedies were able to have a “biological
effect” upon the human body.
In 2004, we signed a contract with Mr Randi and started to
work on a protocol devised by a group of internationally re-
puted experts. After working for four years to arrange every-
thing for such an experiment, including the cooperation of a
Greek public hospital where the experiment would have tak-
en place, when finally everything was in place and the exper-
iment was to begin, Mr Randi suddenly WITHDREW from the
agreement in a totally unacceptable manner. For those who are
interested in reading the details of this story, please go to the
following link: http://www.vithoulkas.com/clinical-trial-randi.
If it is necessary to formulate a concept for the active princi-
ple in relation to potentized water, a much more meaningful
and useful concept is this:
after a process of serial dilutions and potentiations, the wa-
ter becomes “biologically active”, and this is the most im-
portant issue.
Whether the water has memory or not is totally irrelevant for
homeopathy.
References:
1. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC534457/
2. http://www.nature.com/news/2004/041004/full/news041004-19.html
3. Davenas E, Beauvais F, Amara J et al: Human basophil degranulation trig-
gered by very dilute antiserum against IgE. Nature, 1988; 338: 816–18
4. http://www.i-sis.org.uk/electromagneticSignalsFromHIV.php
5. http://www.sciencemag.org/news/2014/09/unesco-host-meeting-
controversial-memory-water-research
6. https://www.theguardian.com/science/2007/nov/16/sciencenews.g2
7. https://www.theguardian.com/commentisfree/2015/mar/12/
no-scientific-case-homeopathy-remedies-pharmacists-placebos
8. http://news.bbc.co.uk/2/hi/health/7505286.stm
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10. http://content.time.com/time/magazine/article/0,9171,149840,00.html
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work.html
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Will-lawsuits-spell-the-end-of-homeopathy/1
13. http://www.tcm.phy.cam.ac.uk/~bdj10/water.memory/milgrom.html
14. https://www.newscientist.com/article/dn3817-icy-claim-that-water-
has-memory/
15. http://www.badscience.net/2007/08/490/
16. http://www.badscience.net/2007/08/the-memory-of-water-is-a-reality/
17. http://www.badscience.net/2000/01/journal-club-the-history-of-the-
memory-of-water/
18. http://www.chem.uw.edu.pl/people/Dzwolak/dzwolak_ang.pdf
19. https://www.newscientist.com/article/mg12316732.900-benveniste-
suspended-for-damaging-institutes-image/
20. https://www.amazon.com/The-Memory-Water-Homoeopathy-Science/
dp/0722535341
21. http://www.atomsandnumbers.com/2013/can-we-please-forget-about-
water-memory/
22. http://www.health24.com/Natural/News/Can-water-remember-20120721
23. http://www.ncbi.nlm.nih.gov/pubmed/2455869
24. http://www.nytimes.com/1988/07/27/us/water-that-has-a-memory-skep-
tics-win-second-round.html
25. Belon P, Cumps J, Ennis M et al: Histamine dilutions modulate basophil ac
-
tivation. Inflamm Res, 2004; 53: 181–88
26. http://www.bbc.co.uk/science/horizon/2002/homeopathy.shtml
27. Ibid., 6–22
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... The opinion that the experiments of Jacques Benveniste 19 were erroneous or ill-founded may be encountered even among people from the homeopathic community. 20 However, we believe that the verification of these experiments by Jean Sainte-Laudy, Madeleine Ennis and others, 21,22 despite the subsequent equivocal results of different scientific teams in their attempts to replicate that outcome, renders the picture very complex, as well as open to alternative explanatory hypotheses. First, we have to note that the research groups of Benveniste and Ennis already had an outstanding reputation and record in the scientific community. ...
... In a recent article referring to the Benveniste case, 20 Vithoulkas stated that, from the very beginning, he considered Benveniste's attempts for in vitro experimentation with UHDs incompatible with the principles of homeopathy. A main point in Vithoulkas' objection is: 'A high potency can never bring about a structural change in the organism, like the one Benveniste claimed'. ...
... 41 Non-monotonic and hormesis-like responses, as well as oscillations, are indications of the highly non-linear and complex character of organisms and cellular systems, and very probably of the homeopathic phenomenon itself. 42 On closer examination of the similia principle itself, claimed by Vithoulkas as contrary to the whole concept behind Benveniste's experiment, 20 it is well known that several homeopathic remedies (Chamomilla, Arnica, Hypericum, to cite only a few) cure the same ailments or symptoms as those for which the mother tinctures (used in their preparation) are used. The formulation of the similia principle verified by homeopathic experience is: 'The more complete is the similarity between a patient's symptoms and the remedy picture during homeopathic pathogenetic trials (HPTs, provings), the more effective the remedy will be when prescribed to this patient'. ...
Article
We discuss questions related to the ‘Benveniste Affair’, its consequences and broader issues in an attempt to understand homeopathy. Specifically, we address the following points: 1. The relationship between the experiments conducted by Benveniste, Montagnier, their collaborators and groups that independently tested their results, to ‘traditional’ homeopathy. 2. Possible non-local components such as ‘generalised entanglement’ as the basis of the homeopathic phenomenon and experimental evidence for them. 3. The capability of highly diluted homeopathic remedies to provoke tangible biological changes in whole organisms and cellular experimental systems. 4. Aspects of the similia principle related to the above. 5. Suggestions that can lead to experimental verifications of the non-local hypothesis in homeopathy.
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When human polymorphonuclear basophils, a type of white blood cell with antibodies of the immunoglobulin E (IgE) type on its surface, are exposed to anti-IgE antibodies, they release histamine from their intracellular granules and change their staining properties. The latter can be demonstrated at dilutions of anti-IgE that range from 1 x 10(2) to 1 x 10(120); over that range, there are successive peaks of degranulation from 40 to 60% of the basophils, despite the calculated absence of any anti-IgE molecules at the highest dilutions. Since dilutions need to be accompanied by vigorous shaking for the effects to be observed, transmission of the biological information could be related to the molecular organization of water
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Full-text available
In order to demonstrate that high dilutions of histamine are able to inhibit basophil activation in a reproducible fashion, several techniques were used in different research laboratories. The aim of the study was to investigate the action of histamine dilutions on basophil activation. Basophil activation was assessed by alcian blue staining, measurement of histamine release and CD63 expression. Study 1 used a blinded multi-centre approach in 4 centres. Study 2, related to the confirmation of the multi-centre study by flow cytometry, was performed independently in 3 laboratories. Study 3 examined the histamine release (one laboratory) and the activity of H(2) receptor antagonists and structural analogues (two laboratories). High dilutions of histamine (10(-30)-10(-38) M) influence the activation of human basophils measured by alcian blue staining. The degree of inhibition depends on the initial level of anti-IgE induced stimulation, with the greatest inhibitory effects seen at lower levels of stimulation. This multicentre study was confirmed in the three laboratories by using flow cytometry and in one laboratory by histamine release. Inhibition of CD63 expression by histamine high dilutions was reversed by cimetidine (effect observed in two laboratories) and not by ranitidine (one laboratory). Histidine tested in parallel with histamine showed no activity on this model. In 3 different types of experiment, it has been shown that high dilutions of histamine may indeed exert an effect on basophil activity. This activity observed by staining basophils with alcian blue was confirmed by flow cytometry. Inhibition by histamine was reversed by anti-H2 and was not observed with histidine these results being in favour of the specificity of this effect We are however unable to explain our findings and are reporting them to encourage others to investigate this phenomenon.