The effect of hydrochloric acid, tetragastrin, and cimetidine, a H2-receptor antagonist, on endogenous prostaglandin E2 (PGE2) and prostacyclin (PGI2) in rat gastric mucosa was investigated. Intragastric instillation of 0.25 N HCl increased PGE2by about 2 times in both fundic and antral mucosa, and inhibited ulcer formation induced by subsequent instillation of a necrotizing agent (0.6 N HCl) . Tetragastrin (4 μg/kg, subcutaneously) also increased PGE2and PGI2in both fundic and antral mucosa 15 minutes after administration, and also inhibited ulcer formation induced by subsequent instillation of 0.6 N HCl. Cimetidine in a non-antisecretory dose (2 mg/kg, intraperitoneally) exerted no effect on endogenous PGE2, while in an antisecretory dose (100 mg/kg), the agent decreased PGE2by 72% in fundic and 84% in antral mucosa. These results suggest that acid induces those cytoprotective PGs and enhances mucosal integrity.