Somatostatin, a tetradecapeptide with potent inhibitory actions on gastric acid secretion, potentiated carbamylcholine-induced synthesis and release of prostaglandin E2 from isolated perfused rat stomachs. The ability of somatostatin to inhibit acid secretion was blocked by indomethacin, an inhibitor of prostaglandin synthesis. These results suggest that prostaglandins mediate gastric acid inhibition by somatostatin in the rat.