A variety of stimuli can act through the central nervous system to alter gastric acid secretion. Lesioning and stimulation experiments have established roles for the lateral and ventromedial hypothalamus and the limbic system in the central regulation of gastric acid secretion. Recently a number of neuropeptides have been demonstrated to alter gastric acid secretion after central administration. Thyrotropin-releasing hormone (TRH) and gastrin both increase gastric acid secretion, whereas bombesin, calcitonin, the endogenous opioid peptides and neurotensin decrease gastric acid secretion. With the exception of bombesin, all the other neuropeptides appear to produce their effects through a vagally mediated mechanism. In addition, a number of these neuropeptides, when centrally administered, have been demonstrated to exert a potent cytoprotective effect against stress ulcer development. This review develops a peptidergic hypothesis of gastric acid secretion, suggesting that the final integration of the cephalic phase of gastric acid secretion is brought about by maintaining a delicate balance in the concentration of a number of interacting peptides and monoamines.