The effect of rat amylin on acid gastric secretion in the pylorus-ligated, unanesthetized rat system (Shay test) was examined. Amylin administered peripherally (2.5, 5, 10, 40, 100, or 160 micrograms/kg, SC) or intracerebroventricularly (1.5, 2.7, or 5 micrograms/rat, ICV) decreased acid gastric secretion in a dose-dependent manner. Central administration of amylin gave a stronger suppression of gastric secretion than peripheral injection. In addition, ICV-injected amylin inhibited insulin-stimulated acid gastric secretion and was effective in suppressing acid gastric secretion in rats depleted of somatostatin by pretreatment with cysteamine. This study suggests that amylin may participate in the central regulation of acid gastric secretion and indicates a possible biological function of amylin as a gastrointestinal peptide.