Luminal gastric acid is essential for the formation of acute gastric mucosal lesions during ischemia. The mechanism by which luminal acid promotes gastric injury is, however, unclear. We investigated the effect of exogenous luminal acid on gastric mucosal blood flow using the radiolabeled microsphere technique. In rats with intact gastric blood supply application of exogenous luminal acid increased blood flow to the mucosa of the corpus and antrum. However, after ligation of the left gastric artery, which compromised mucosal blood flow to the corpus, application of luminal exogenous acid further decreased blood flow to the corpus. This indicates that the ability of the normal stomach to respond to luminal acidification with an increase in blood flow, which is thought to support clearance of back diffusing H+, is reversed in the ischemic stomach. The exposure to high luminal H+ concentrations may therefore promote gross injury in the ischemic stomach by further compromising nutritional mucosal blood flow.