Although gastric bleeding is a complication of renal failure, little is known about the causative factors. The possible mechanistic role of metabolic acidosis was studied in rats made acidotic by ingestion of 1.6% ammonium chloride. Since patients with renal failure may be in a stressed condition, the number of gastric lesions produced was studied in rats with and without seven hours of restraint stress. When arterial blood pH was reduced to 7.26, metabolic acidosis had no effect on the stomach. With a pH of 7.17, there was an increase in the number of gastric erosions in rats with restraint. Acidosis had no effect on gastric acid production or equilibration, on in vitro oxidative metabolism of gastric mucosa, or on gastric morphologic features in noneroded areas. These studies suggest that metabolic acidosis may account in part for gastric lesions associated with renal failure.