AbstractThe lining of the stomach of man is protected from its unique secretion, hydrochloric acid, by a variety of highly specialized characteristics. Foremost is its relative impermeability to hydrogen ions. The gastric surface epithelial cell which forms a continuous integument from the esophagus to the duodenum plays an important role in this barrier function. Disruption of the barrier by injurious agents, sepsis, or shock may lead to severe erosive gastritis when acid is present within the lumen of the stomach. This process is accelerated during periods of low mucosal blood flow. The relationship of the rate of back‐diffusion of hydrogen ions to mucosal blood flow appears critical. Factors which (a) inhibit acid secretion, (b) strengthen the barrier to H+ diffusion, or (c) increase mucosal blood flow will protect the stomach from injury. Prostaglandins of the A, E, and F series offer a level of protection in experimental erosive gastritis that is out of proportion to their effect on acid secretion and mucosal perfusion. The secretion or filtration of an alkaline secretion may be an important component of the cytoprotection which follows the topical exposure of gastric mucosa to 16,16‐dimethyl (PGE2). The role of mucus release in this situation requires further elucidation.