Exposure of the mucosal surface of exteriorized chambered fundic segments of dog stomach to p-chloromercuribenzene sulfonate (PCMBS) resulted in predictable gross and microscopic structural changes. The first visible response after PCMBS (10 mM) in isosmotic HCl was an intense release of periodic acid-Schiff-stainable mucus. Within 2 min, radioactive PCMBS was found within cells along the entire depth of the gastric glands. Surface cells at 15 min revealed vacuolization of the cell cytoplasm, dilation of the perinuclear and intercellular spaces, mitochondrial swelling, loss of microvilli, and plasmalemma irregularities. Tight junctions, Golgi, and mucous granules appeared unaltered. However, in advanced injury, mucous granules became less dense and their membranes, which were usually smooth, became fragmented and convoluted at this point. Necrotic parietal cells were extruded into the lumen. Damage, however, only rarely extended into the deeper glandular and connective tissue areas.