Studies to date indicate that certain synthetic prostaglandin E derivatives, notably misoprostol and enprostil, possess duodenal ulcer healing efficacy that is equivalent to that of the existing H2-receptor antagonists. Whether healing is achieved by virtue of their antisecretory action alone or in combination with their cytoprotective properties cannot be ascertained. Earlier reports that non-antisecretory prostaglandin E2 was effective for duodenal-ulcer healing suggested that cytoprotective mechanisms may contribute to ulcer healing, but this needs be confirmed. Chronic cigarette smoking adversely affects duodenal ulcer healing despite treatment with potent acid-reducing regimens. Evidence is available that cigarette smoking reduces luminal prostaglandins in the stomach, and that misoprostol, a prostaglandin E1 is able to overcome the adverse effect of smoking on duodenal ulcer healing, further suggesting that cytoprotective mechanisms may contribute to ulcer healing. Furthermore, misoprostol has been shown to be the first therapeutic agent capable of improving active chronic antral gastritis, which has recently been found to be almost invariably associated with active duodenal ulcer.