Misoprostol, a prostaglandin E1 analogue was administered orally to male volunteers in doses of 50, 100, 200 and 400 mcg and its effects on gastric secretion compared with those observed following placebo. All doses significantly inhibited basal acid secretion by up to 98% and also inhibited histamine-stimulated secretion during the first 60 minutes of stimulation. Only the 50 mcg dose did not cause a significant reduction in acid output over the entire 2 hour period of histamine stimulation. The effect on gastric secretory volume was much less than that on acid, and in general the reductions were not statistically significant. Pepsin concentration was reduced during basal secretion only. Misoprostol is a potent inhibitor of basal acid secretion and moderately inhibits histamine-stimulated acid secretion with a duration of action of at least three hours following drug ingestion.