Cimetidine, like its predecessors burinamide and metiamide, has been shown in vitro to be a specific competitive histamine H2-receptor antagonist. In vivo, it is a potent inhibitor of histamine-stimulated gastric acid secretion in animals and man after both intravenous and oral administration. Doses sufficient to inhibit gastric secretions are without measureable effects on other physiologic systems. The main indication for cimetidine is in the treatment of duodenal ulcer and of the Zollinger-Ellison syndrome. Useful indications are treatment of gastric ulcer and pnacreatic insufficiency. Possible indications are prevention of gastrointestinal bleeding and treatment of peptic esophagitis. The neutrophil toxicity seen with metiamide has so far not been demonstrated with cimetidine; side effects with cimetidine have generally been trivial. In the future, H2-receptor antagonists are likely to become key therapeutic agents in diseases in which gastric acid-pepsin secretion plays a pathogenetic role.