Histamine is formed by decarboxylation of the amino acid histidine and is found both in plants and in animals, including man. In man it has important biologic functions. To assess the physiologic role of histamine, however, it is necessary to have a reliable and convenient method to determine its concentration in biologic fluids and tissue. Histamine has been determined by bioassay, chemically by different modification of a fluorometric method, by radioenzymatic methods, and, recently, by immunoassays. Immunoassay of histamine has, however, been difficult to establish, mainly as a result of problems with the production of an antibody with histamine specificity. This is due to the general occurrence of histamine in all animal species. By binding histamine to different ligands, several researchers have succeeded in producing antibodies against antigens in which histamine is integrated. Treating samples and histamine standard with the same coupling agent, reliable and specific radioimmunoassays of histamine have been established. We have for some years utilized a commercial radioimmunoassay of histamine and confirmed its convenience, specificity, and sensitivity. In some patients taking a histamine-2 blocker (cimetidine or ranitidine) we have detected an increase in plasma histamine which also tended to be increased after proximal gastric vagotomy and in patients with gastric ulcer compared with patients with duodenal ulcer. In rats treated with high doses of omeprazole for 90 days we found an increase in the enterochromaffin-like cell mass and in histamine concentration in the oxyntic mucosa which was reflected by an increase in plasma histamine.(ABSTRACT TRUNCATED AT 250 WORDS)