Histamine is not uniformly distributed in the human and animal organisms, but occurs in high concentrations in the gastric mucosa. The enzymes responsible for its metabolism--histidine decarboxylase, histamine N-methyltransferase and diamine oxidase--seem to be less predominantly localized in the stomach. Considerable effort was necessary to detect and measure histamine formation in the gastric mucosa. This was a controversial subject that only was solved recently. Histamine inactivation by histamine methyltransferase occurs in man in the fundic gastric mucosa that has reasonable enzymic activity. However, liver, spleen and intestine show much higher activities indicating less specificity of histamine catabolism in the gastric mucosa. Finally, diamine oxidase activity was once thought to be absent in the corpus mucosa, but more recently, moderate activities of this enzyme were found in several species, including man. Thus, histamine metabolism in the gastric mucosa is by no means unique in mammalian tissues, but the presence of these enzymes may be regarded as an indicator of its physiological function. To some extent enzymic activities involved in histamine formation and inactivation are regulated in the process of acid secretion. Histidine decarboxylase and histamine N-methyltransferase activities are enhanced by gastrin, but are not influenced by vagal stimulation. Hitherto, only histamine methylation was found to be diminished in duodenal ulcer disease. Vagotomy and histamine H2-receptor antagonists modulate histamine catabolism by histamine methyltransferase. The implication of these findings for treatment of duodenal ulcer are discussed.