E-type prostaglandins inhibit gastric acid secretion and stimulate gastroduodenal bicarbonate and mucus secretion as well as the formation of hydrophobic surfactant-like phospholipids in the gastric epithelial cells. Furthermore, E-type prostaglandins have trophic effects on the gastro-duodenal mucosa. These effects may partly explain the unique protective effects of E-type prostaglandins against experimental damage of gastroduodenal mucosal lesions in animals and humans. E-type prostaglandins have been used in clinical trials on peptic ulcers, on upper gastrointestinal bleeding, and on mucosal lesions induced by non-steroid anti-inflammatory drugs. In nearly all trials natural prostaglandin E₂ as well as the synthetic prostaglandin analogues arbaprostil, misoprostol, enprostil, rioprostil, trimoprostil, and rosaprostol accelerated the healing of peptic ulcers compared with placebo. The PGE analogues must be given in gastric acid antisecretory dosage to reach healing rates similar to those of cimetidine. The drugs seem to be safe, and diarrhoea—the main adverse effect—occurs rarely. Future studies are necessary to identify the place of prostaglandins among other drugs used in peptic ulcer treatment. In the treatment of acute upper gastrointestinal bleeding, arbaprostil was not more effective than placebo in spite of several case reports suggesting that prostaglandin E analogues would be helpful in these situations. E-type protaglandins were effective in preventing gastroduodenal mucosal lesions caused by non-steroid anti-inflammatory drugs, but the long-term efficacy of prostaglandins has to be established in studies on patients under continuous anti-inflammatory treatment.