The present series of studies were performed to test the hypothesis that ethanol in the blood may play a role in the pathogenesis of gastric mucosal injury. Another hypothesis to be examined was that endothelin may be involved in ethanol-induced gastric mucosal injury. Elevated levels of blood ethanol induced by intraperitoneal infusion of ethanol increased vulnerability of the stomach to hydrochloric acid in a dose-dependent manner in rats. This may be due to impaired gastric mucosal hemodynamics and oxygenation as demonstrated by the results obtained by organ reflectance spectrophotometry (decreases in indices of mucosal hemoglobin contents and hemoglobin oxygen saturation). Ethanol infusion caused a dose-dependent increase in gastric vascular resistance in perfused rabbit stomach, which was accompanied by an increased production of endothelin-1. The results suggest that endothelin may be involved in the pathogenesis of ethanol-induced gastric mucosal injury.