The abilities of antacid (Mylanta II), sucralfate, cimetidine, and ranitidine to protect the gastric mucosa against ethanol-induced necrosis were compared in a standardized, experimental rat model. Fasted rats received pretreatment with either saline, Mylanta II, 500 mg/kg of sucralfate, 50 mg/kg of cimetidine, or 50 mg/kg of ranitidine. This was followed one hour later by intragastric administration of 2 ml of 100 percent ethanol. Gastric mucosal injury was assessed four hours after administration of ethanol by quantitation of gross mucosal necrosis, assessment of mucosal histology, and determination of intragastric blood and protein concentrations. Pretreatment with Mylanta II or sucralfate significantly reduced ethanol-induced gastric mucosal necrosis. The protective effect of sucralfate was six to 10 times greater than that of Mylanta II. H2-receptor antagonists increased ethanol-induced gastric mucosal necrosis.