The importance of HDL-cholesterol determination for assessing the risk of coronary heart disease in individual cases is discussed on the basis of precision and specificity studies of the most commonly used precipitation method and the results obtained by this method in epidemiological and clinical studies. The lack of precision and the poorly defined specificity of this method make it difficult to evaluate the clinical and epidemiological data. Diagnoses which are often not quite clear and the fact that differences in the HDL-cholesterol concentrations are only slight between patients with coronary heart disease and healthy controls, as well as the low ability of any given HDL-cholesterol marginal value to distinguish between risk and non-risk probands in a group, make it impossible to recommend the labor-intensive and very expensive HDL-cholesterol determination test for screening purposes. The assumption that the HDL-cholesterol concentration is of greater value than the LDL-cholesterol level in assessing the risk for coronary artery disease is based on the study of a group of relatively old probands over 50 yr of age) which was followed for only four years. Similar results for younger groups do not exist. For this reason and also because of the different determination methods, the marginal HDL-cholesterol values applicable to this group only to a limited extent cannot be generalized for the Federal Republic of Germany. In our opinion, distinct guidelines for the isolated evaluation of HDL-cholesterol concentrations in the individual case can only be established when it is known on which lipoproteins of the heterogenous HDL class the assumed protective effect is based, and by which method they can be precisely measured. For this purpose, extensive prospective studies and clinical studies are required in which the plasma lipoproteins of definitely diagnosed collectives should be measured as precisely as possible by as many different methods as possible. As far as quality control of some of the methods is concerned, this has been greatly facilitated, and in part only become possible through commercial kits and the use of a control serum for human lipoproteins.