The synthetic prostanoid, Ro 22-6923, was studied for its effects on canine gastric secretion. Histamine-stimulated acid secretion was inhibited for up to 8 hr after an orally administered dose of 0.25 mg/kg Ro 22-6923. In the Amdrup (modified Pavlov) pouch model, Ro 22-6923 significantly inhibited food-stimulated acid secretion at an oral dose of 0.5 mg/kg. The effect lasted for 4 hr and was of greater intensity than that observed with 5 mg/kg cimetidine. The ED50 for Ro 22-6923 in this model was 0.25 mg/kg and 0.09 mg/kg for oral and intrapouch administration, respectively. Natural prostaglandin E2 was inactive up to 1 mg/kg orally, but had an ED50 of 0.08 mg/kg when administered directly into the pouch. The results indicate that Ro 22-6923 is a potent, long-acting antisecretory drug that may be useful in the therapy of peptic ulcer disease in man.