In a series of rats whose histamine formation was blocked by either pyridoxine deficiency or decarboxylase inhibition with 4-bromo-3-hydroxybenzy-oxyamine dihydrogen phosphate (NSD-1055), we found that basal and gastrin-stimulated gastric secretion was markedly lowered. Histamine stimulation, however, was an effective stimulus in these inhibited rats. Vagal-induced acid secretion through insulin hypoglycemia and direct parasympathomimetic stimulation with bethanechol, the parasympathomimetic drug, were also not blocked in these animals. These results suggest that, at least in the rat: (1) histamine may be an important endogenous chemostimulator of gastric secretion; (2) gastrin stimulates the parietal cell directly through histamine release; and (3) vagal stimulation apparently utilizes, in part at least, a mechanism other than histamine release.