1 The potency and selectivity of action of prostaglandin E2 and its (15S)- or (15R)-15 methyl and 16, 16 dimethyl analogues on gastrointestinal function have been studied in the rat. 2 The (15S)-15 methyl and 16, 16 dimethyl analogues were 40 times as active as prostaglandin E2 in inhibiting pentagastrin-stimulated acid secretion on intravenous administration to the anaesthetized rat, and 100 times as active on subcutaneous injection to the chronic fistula rat. 3 In antisecretory doses, the analogues, like prostaglandin E2, caused bile reflux and, in higher doses, profuse diarrhoea. 4 The (15S)-15 methyl and 16, 16 dimethyl analogues were at least 30 times as active as prostaglandin E2 in causing changes in intestinal intraluminal pressure in vivo, but were equipotent on isolated smooth muscle. 5 In equivalent antisecretory doses, the methyl analogues had little effect on systemic arterial blood pressure and resting mucosal blood flow compared with prostaglandin E2. 6 The (15R) methyl epimer administered parenterally had little effect on gastrointestinal function but brief acid incubation greatly increased its activity.