The influence of intraarterial infusion of hydrochloric acid on gastric mucosal injury induced by topical bile salts was assessed in a canine ex vivo model. Exposure of the gastric mucosa to 5.0 mM sodium taurocholate in acid bathing solution alone resulted in a slight but not significant reduction in intramural pH of gastric mucosa and mild mucosal damage. When hydrochloric acid (0.1 N) was infused directly into the artery perfusing the stomach of the dogs, the intramural pH of gastric mucosa markedly decreased. The mucosal acidification was associated with severe ulcers in all test dogs that received intraarterial infusion of hydrochloric acid. The deleterious effect of intraarterial infusion of hydrochloric acid was not due to ischemia since the gastric blood flow remained relatively unchanged. The severe mucosal ulcerations were perhaps caused by the decrease in the ability of gastric blood to buffer the incoming luminal acid induced by topical bile salts. These results suggest that (1) the pH of arterial blood perfusing the stomach may also be an important determinant in the ability of the gastric mucosa to protect itself against acid injury, and (2) better management of systemic acid-base balance may contribute to a lower incidence of stress ulcers in critically ill patients.