1. Gastric acid and pepsin secretion stimulated almost maximally by i.v. infusion of histamine, the mucosal blood flow, and the immunoreactive prostaglandin E (PGE) content have been measured following arachidonic acid administration either intra-arterially or topically to the mucosa of the fundic portion of a stomach kept in a Lucite chamber. 2. Arachidonic acid administered directly to the stomach produced a marked and significant inhibition of histamine-induced gastric secretion accompanied by a reduction in mucosal microcirculation and a rise in the immunoreactive PGE content in the gastric juice. 3. These secretory and circulatory changes induced by arachidonic acid were prevented by pretreatment of the gastic mucosa with indomethacin, a potent inhibitor of the prostaglandin synthetase system. 4. Arachidonic acid infused intra-arterially in graded doses resulted in a dose-dependent reduction in gastric acid secretion, mucosal blood flow and cyclic AMP mucosal content. 5. These studies indicate that arachidonic acid applied directly to the stomach causes a marked gastric secretory inhibition, probably due at least in part to the enzymic transformation of arachidonic acid to prostaglandins and possibly other active lipids responsible for the changes in the gastric mucosal microcirculation and cyclic AMP mucosal content.