Several neuropeptides injected intracisternally were assessed for their effects on gastric secretion in rats.Bombesin (1 #g) completely suppressed gastric acid secretion, reduced the volume of gastric secretion, and partially blocked insulin-or 2-deoxy-D-glucose-induced stimulation of gastric acid output. The inhibitory effect of this peptide is dose-dependent, long-acting, reversible, and specific. Bombesin response appears to be central nervous system-mediated; its expression is not dependent on the vagus nerve or the adrenal glands, and does not rely on a decrease in gastrin secretion. Among seven other peptides tested, only 19-endorphin and a potent gonadotropin releasing-factor (gonadoliberin) agonist significantly reduced gastric acid secretion, with an activity ca. 100 times less than that of bombesin. The presence of bombesin-like material in rat brain and the high potency of bombesin to inhibit gastric secretion suggest that this peptide may be of physiologic significance as a chemical messenger involved in brain modulation of gastric secretion. The original observation that discrete brain lesions induced pathological changes in the gastric mucosa (1, 2) focused attention on the role of the central nervous system in the pathophysiological regulation of gastric function. Subsequently, numerous investigators attempted to elucidate brain structures and neurogenic/humoral pathways involved in the control of gastric secretion. In rats, several studies have demonstrated that the hypothalamus influences gastric secretion. Stimulation of the lateral hypothalamus, but not of the surrounding area, caused a vagally mediated increase in acid output (3, 4). On the other hand, stimulation of the ventromedial hypothalamus decreased acid secretion (3), whereas lesion experiments had opposite effects (5). Previous studies of chemical signals participating in the brain modulation of gastric secretion seem to indicate that cholinergic-stimulatory (6) and noradrenergicinhibitory mechanisms play a role (4, 7).The presence in mammalian brain of oligopeptides acting in the central nervous system to influence glucoregulation (8, 9), thermoregulation (10, 11), blood pressure (12, 13), sympa-