Interleukin-1 beta (IL-1 beta) has been reported to stimulate prostaglandin synthesis by the rat stomach in vitro and to inhibit gastric acid secretion in vivo. We have therefore tested the hypothesis that IL-1 beta might have protective actions in experimental models of gastroduodenal ulceration. IL-1 beta, given i.p., dose and time dependently reduced the severity of ethanol-induced gastric damage. A pretreatment time of 90 min was found to produce the greatest reduction of damage, while doses of 0.1 micrograms/kg or greater were found to produce significant effects. The protective actions of IL-1 beta were abolished by prior boiling or by pretreatment of the animals with indomethacin, and were not shared by the nonapeptide fragment 163-171. IL-1 beta also reduced the severity of gastric damage induced by indomethacin and the duodenal ulceration induced by cysteamine. The results indicate that IL-1 beta has protective actions in three separate experimental models of gastroduodenal ulceration. The mechanism of action of IL-1 beta is not entirely clear, but contributions of endogenous prostaglandin synthesis and inhibition of gastric acid secretion cannot be excluded.