Using a specific fluorimetric and biological method, the occurrence and distribution of histamine was investigated in man, various mammals, birds, reptiles, amphibians, bony and cartilaginous fishes, lancelets, tunicates, echinoderms, molluscs, and crustaceans. The amine was identified by the fluorescence spectrum, by specific antihistaminics in the bioassay, by the comparison of the fluorimetric histamine values following three different isolation procedures, and in some tissues also by thin-layer chromatography. Histamine was found in all chordates in considerable concentrations with the exception of the stomachless carp. The distribution of histamine in the body, however, varied largely from species to species. Only the gastric mucosa of all vertebratesinvestigated was relatively rich in histamine. The amine was nearly uniformly distributed in amphibians and fishes, in which only the stomach and partly the intestinum showed higher histamine concentrations than all the numerous other tissues investigated. The distribution of histamine, however, in mammals, birds, and reptiles showed great variations from tissue.to tissue. Organs free from histamine were first found in fishes going backward in the phylogeny. Because of the great variabilities in the distribution of histamine in the body of numerous species which were studied in this investigation, only one hypothesis can be developed with respect to a common physiological significance of histamine: there is a selective accumulation of histamine in the gastric mucosa of all chordates possessing acid-secreting cells and a low concentration of histamine in the gastro-intestinal tract of stomachless fishes. The gastric acid secretion is stimulated by histamine in all vertebrates investigated, whereas in many fishes histamine has no effects on the circulation or on smooth muscles of the gastro-intestinal tract or on the uterus. Thus, stored histamine probably has a specific function in the gastric mucosa, but not a general function, such as the regulation of ubiquitous metabolic processes or the regulation of microcirculation.