Although exact numbers on the prevalence of histamine intolerance are lacking, it seems to be on a rise during the last years. The estimated prevalence in the population is 3%. This is particularly true for middle-aged female patients. A deficiency of 1 of the histamine metabolizing enzymes, diamine oxidase (DAO) has been postulated as the main causal factor. Recently, a commercial radioimmunoassay for determination of DAO activity has been launched. To evaluate the clinical impact of this assay for the diagnosis of histamine intolerance, we performed a prospective, multicentre study in 207 adult patients. In 77 patients, a diagnosis of histamine intolerance was made based on clinical criteria, in 67 a diagnosis "in question", and 61 healthy patients without anamnestic evidence for histamine intolerance served as a control. Interestingly, no correlation between diamine oxidase serum levels and clinical status could be found in any of the 3 groups. We, therefore, recommend further investigations, before determination of DAO serum activity should be used as a screening tool for the diagnosis of histamine intolerance.