Topical application of "barrier breakers," including drugs such as aspirin and ethanol, produces widespread destruction of the surface epithelium of the stomach. Such damage does not usually develop into hemorrhagic erosions because the integrity of the surface epithelium is reestablished within a few minutes to hours by the process of epithelial restitution. This process involves active migration of cells from the gastric pits and upper regions of the glands. Restitution is independent of cell division but probably requires an intact basal lamina (basement membrane). The process also depends, in vivo, on adequate microvascular perfusion and can be prevented by high local concentrations of acid. Prostaglandins do not appear to directly affect the restitution process. It is unlikely that prostaglandins either "cytoprotect" the epithelium or accelerate the rate of epithelial migration. Exogenous prostaglandins can, however, protect against the development of hemorrhagic erosions by maintaining an environment in which restitution can proceed. By preventing disruption of the mucosal microvasculature, prostaglandins ensure that the migrating epithelial cells are provided with nutrients and oxygen necessary for cellular activity.