The effect of interleukin-1 (IL-1) on gastric secretory functions was examined in pylorus-ligated conscious rats. Intracisternal (i.c.) injection of IL-1β (1–100 ng) induced dose-related, long-lasting inhibition of gastric acid output, which was due to the reductions of both the amount and the acid concentration of the gastric juice. A much higher dose of IL-1α was required to achieve identical effects on gastric acid secretion when it was given by intravenous routes. The i.c. injection of IL-1α also had an inhibition of gastric secretion. This inhibitory effect of i.c. applied IL-1β on gastric acid secretion was completely abolished in indomethacin-pretreated animals but not in reserpine-pretreated ones. These results suggest that IL-1 may have an inhibitory action on the regulation of gastric secretory functions by its central action which is dependent on the eicosanoid metabolism.