The synthesis and gastric antisecretory activities of the delta 4,5-cis, delta 4,5-trans, and 4,5-acetylenic analogues of 15-deoxy-16-hydroxy-16-methyl prostaglandin E1 methyl ester are described. The key step in the preparation of these compounds involved the stereospecific conjugate addition of a cuprate reagent to the appropriate cyclopentenones. Although the trans and acetylenic derivatives were weak inhibitors of gastric acid secretion, the cis olefin was more potent and longer acting than the saturated parent compound. Selectivity with respect to unwanted diarrheagenic effects was found to be improved over that of both the parent 16-hydroxy compound and the reference standards, (15S)-15-methyl- and 16,16-dimethylprostaglandin E2.