To evaluate the effect of arachidonic acid (AA), a prostaglandin precursor, on the mucosal level of PGE2 and its possible protective role against stress ulcerations, 40 Holtzman rats were divided into four groups: Group I intragastrically receiving 1 ml of normal saline (NS); Group II, NS pretreatment followed by stress; Group III, intragastric AA pretreatment without stress; and Group IV, intragastric AA followed by stress. AA was administered as a 120 mM solution in a nonionic detergent, adjusted to a pH of 8.0. Stress was provided by the cold-restraint method. After sacrifice, the number of gastric mucosal ulcerations were counted. Specimens of nonulcerated mucosa were assayed for PGE2 by derivatization with panacyl bromide and by using high-performance liquid chromatography. The animals in Groups I, III, and IV developed no gastric ulcerations and their mucosal prostaglandin E2 remained at a normal level, while those in Group II had a significant reduction of mucosal PGE2 (P less than 0.05) and a significantly increased number of gastric ulcerations (P less than 0.002). These data indicate that stress-induced mucosal ulcerations are associated with significant decreases in the gastric mucosal levels of PGE2. Intragastric administration of arachidonic acid prevents the formation of stress mucosal ulcerations and maintains a normal level of mucosal PGE2.