1 We studied the effects of intracerebroventricular (i.c.v.) administration of prostanoid EP receptor ligands on vagally stimulated gastric acid secretion in rats anaesthetized with urethane.2 Administration of misoprostol (EP3/EP2 receptor agonist) and sulprostone (EP3/EPj receptor agonist) reduced vagally mediated gastric acid secretion in a dose-dependent manner (0.1, 0.3 and 1.0 nmol per animal). Butaprost (EP2 receptor agonist) (0.3 and 3.0 nmol per animal) was without effect. 17-Phenyl-cotrinor PGE2 (EP1/EP3 receptor agonist) attenuated vagally mediated gastric acid secretion only at its highest dose (1.0 nmol per animal); this antisecretory effect was not prevented by pretreatment with SC-19220 (selective EP, receptor antagonist) (20 nmol per animal, i.c.v.).3 The potency of these test agents in attenuation of vagally mediated gastric acid secretion was as follows: misoprostol > sulprostone > > 1 7-phenyl-co-trinor PGE2> > > butaprost. These results suggest that activation of central prostanoid EP3 receptors induces inhibition of vagally mediated gastric acid secretion in rats.