OPC-12759, 2-(4-chlorobenzoylamino)-3-[2(1H)-quinolinon-4-yl]-propionic acid, was studied for its efficacy to prevent the gastric mucosal damage induced by several necrotizing agents. Experiments were also performed to elucidate the mechanism of this mucosal protective activity. OPC-12759 dose dependently prevented the formation of mucosal necrosis induced by absolute ethanol, 0.2 N NaOH or 0.6 N HCl. PGE2 was also shown to prevent the gastric mucosal erosion induced by necrotizing agents. The mucosal protective effect of OPC-12759 was completely counteracted by pretreatment with indomethacin while that of PGE2 was not. In addition, OPC-12759 given alone increased the generation of gastric mucosal PGE2-like activity. OPC-12759 dose dependently reduced the volume, acid output and pepsin output of the gastric juice in pylorus-ligated rats. The inhibitory effect of OPC-12759 but not of cimetidine or atropine on gastric secretion was also abolished by concurrent administration of indomethacin. These findings suggest that the mucosal protective effect and antisecretory effect of OPC-12759 presumably result from enhancement of the generation of endogenous PGs.