The gastric antisecretory actions of (15S)-15-methyl prostaglandin E2 methyl ester (Me-PGE2) and Prostaglandin E2 (PGE2) were evaluated in the unanesthetized gastric fistula rhesus monkey. Secretion was submaximally stimulated by multiple subcutaneous injections of histamine acid phosphate given every hour for four consecutive hours. When a steady-state plateau of gastric secretion was reached, the PG's were administered as a single bolus dose either intravenously (i.v.) or intragastrically (i.g.). Both PG's inhibited histamine-stimulated gastric secretion. The PG's showed greater sensitivity in inhibiting acid concentration while not affecting volume output. Active i.v. and i.g. antisecretory doses of ME-PGE2 ranged from 3 to 10 mug/kg, while PGE2 showed significant antisecretory activity at i.v. bolus doses of 30-100 mug/kg and i.g. bolus dose of 1.0 mg/kg. Thus, Me-PGE2 is estimated to be at least 10 and 300 times more potent than PGE2 by the i.v. and i.g. administration routes, respectively. These findings indicate that the rhesus monkey shows some similarities to man in responsiveness to gastric secretory inhibition by E-prostaglandins.