The present study was performed to determine if interleukin-1 (IL-1) acts as a chemical messenger in the central nervous system (CNS) regulation of gastric secretion and ulcer formation, using male Wistar rats. The central injection of IL-1 dose-dependently inhibited gastric acid secretion in pylorus-ligated rats at 100 times smaller doses than the peripheral injection of the cytokine. The action of IL-1 was long-lasting because its antisecretory effect was still evident at 8 hr after injection. Furthermore, it was observed that pretreatment with central IL-1 dose-dependently suppressed the development of gastric ulcers induced by water-immersion restraint stress, a well-established ulcerogenic procedure. These results clearly suggested for the first time that IL-1, a cytokine produced by activated monocytes/macrophages, acts centrally in the brain to exert gastric antisecretory and anti-ulcer actions. © 1990 Academic Press, Inc.