Several prostaglandins inhibit gastric acid secretion and prevent ulcer formation in animals by mechanisms that are independent from each other. Little is known about these properties in humans. The effects of 16,16-dimethyl-prostaglandin E2 and the thiaprostaglandin E2 EMD 33 290 were tested on basal acid secretion as well as on the aspirin- and bile salt-induced fall of gastric transmucosal potential difference in man. 16,16-dm PGE2 and EMD 33 290 prevented the drop in gastric potential difference caused by 1000 mg aspirin or 50 ml of 4 mmol/l Na-taurocholate. The protective doses against aspirin were 0.1 microgram and 50 micrograms for 16,16-dm PGE, and EMD 33 290 respectively. Against Na-taurocholate, doses of 1.0 microgram and 250 micrograms were effective. By contrast, 20-100 times higher doses of both prostaglandin analogues were necessary to inhibit gastric acid secretion. Half maximal inhibition of basal acid output was achieved by 0.1 microgram/kg b.w. of 16,16-dm PGE2 and by 28 micrograms/kg b.w. EMD 33 290. In analogy to animal findings, antisecretory prostaglandins protect the human stomach against aspirin and bile salts in doses which are much smaller than the threshold antisecretory ones.