The increased awareness of stress-related mucosal damage SRMD) that accompanied the widespread use of fiberoptic endoscopy and the increased incidence of SRMD that acompanied the advances in caring for critically ill patients resulted in the recognition that the majority of patients in the intensive care unit (ICU) selling will develop mucosal damage. Complications of gastrointestinal hemorrhage in these patients may contribute significantly to their morbidity and mortality, and the consequences of this bleeding may be more severe than the underlying predisposing conditions. Because of the importance of gastric acid in the pathogenesis of SRMD, therapy has focused on reduction if the intraluminal acid concentration. Acid neutralization, while effective, is laborious and associated with side effects. H2-receptor antagonists have been used successfully in the prophylaxis and treatment of SRMD and offer the potential or an effective parenteral as well as oral agent. They obviate the need for frequent antacid administration and eliminate some of the troubles and side effects that accompany in intensive antacid regimen. Of the available H2-receptor antagonists, cimetidine has been the most thoroughly evaluated. It is equivalent to antacids in the prevention of overt bleeding and offers the advantage of dosing flexibility, ease of administration, and a remarkable safety profile. Cimetinine has also been shown to be effective when administered by intermittent bolus infusions given every 8, 6, or 4 h or by primed continuous infusion, which has proven to be the host successful method of controlling intragastric pH. Supralfate protects animal and human gastric mucosa from a variety of injurious agents, but when used in the ICU setting, it has not been shown to be superior to antacids or H2-receptor antagonists. Exogenous prostaglandins and more potent antisecretory drugs such as proton pump inhibitors are other potential agents for the treatment of SRMD, but human studies showing efficacy of these newer agents are limited. Treatment recommendations for these fewer agents must await further clinical trials. Recent trials have suggested that nosocomial pneumonia is less likely to occur in patients treated with sucralfate for SRMD than in those patients given prophylaxis by acid neutralization and/or inhibition. These studies generally failed to separate patients treated with antacids from those treated with H2-receptor antagonists alone. When patients are analyzed by group, the higher incidence of nosocomial pneumonia in the pH-altered patients was primarily seen in the antacid-treated subgroups, suggesting that the increased intragastric volume in these patients is more likely to be a risk factor for pulmonary infection than the elevation in pH. © 1990 Raven Press, Ltd., New York.