We previously reported the prostaglandin analogue SC-29333 [( ~)(16RS)-15deoxy-l6 hydroxy,-16-methyl prostaglandin El methyl ester] to be a potent inhibitor of gastric secretion in animals. SC-29333 is comprised of four stereoisomers in approximately equal proportions. It is believed the major antisecretory activity of SC-29333 results from one isomer, SC-30249 (16S-16-hydroxy-16-methyl, 15deoxy-PGE, methyl ester). Our purpose was to investigate the canine gastric antisecretory action of SC-30249 relative to SC-29333. The studies were carried out in maximally stimulated (histamine) Heidenhain pouch (HP) and gastric fistula (GF) dogs. Administered intravenously (i.v.) to HP dogs at the steady-state plateau of gastric secretion, SC-30249 was found to be approximately three times more potent than SC-29333. Administered intragastrically to GF dogs, SC-30249 is approximately ten times more potent as an inhibitor of gastric secretion than SC-29333. SC-30249 (1 .O pglkg, i.v.) completely inhibited meal-stimulated gastric secretion but had no significant effect on postprandial serum gastrin concentration. SC-30249 shared with SC-29333 the capability of totally antagonizing the histamine-stimulated gastric secretion in HP dogs without reducing gastric mucosal blood flow. These studies indicate that SC-30249 is a potent gastric antisecretory agent that merits clinical evaluation.