To evaluate the relationship between ischemia and disruption of the gastric permeability barrier in the pathogenesis of acute gastric erosions, we studied the effect of (1) hemorrhagic shock, (2) topical application of p-chloromercuribenzene sulfonate (PCMBS), and (3) shock plus PCMBS on total and mucosal blood flow, H⁺ back-diffusion, and mucosal injury in 14 dogs. The fractional distribution of blood flow through the layers of gastric tissue remained unchanged during control, shock, and reinfusion periods. Exposure of the mucosa to PCMBS resulted in a significant increase in H⁺ back-diffusion, which was accompanied by a rise in mucosal blood flow. Hemorrhagic shock alone caused a marked mucosal ischemia without disruption of the permeability barrier. The severest mucosal injury occurs only under experimental conditions where ischemia and increased H⁺ back-diffusion are induced simultaneously. These results suggest that: (1) A cause-effect relationship does not exist between ischemia and barrier disruption in the pathogenesis of acute ulcerations. (2) Mucosal blood flow may play an important role in the disposal of H⁺ permeating the mucosa. (3) The ratio of mucosal blood flow to back-diffusion of H⁺ may determine the degree of mucosal injury.