The effects of esaprazole on gastric secretion (volume, pepsin and acid output) were investigated on animal models, both in vivo and in vitro. In conscious rats whose vagal activity was stimulated by pylorus ligation, esaprazole decreased volume, acid output and pepsin secretion. In anaesthetized stomach-perfused rats, esaprazole inhibited gastric acid secretion evoked by both vagus nerve stimulation or bethanechol infusion. By contrast, on isolated guinea-pig gastric fundus, esaprazole failed to counteract the acid output stimulated by histamine, bethanechol or pentagastrin. In addition to this, phasic contractions evoked by acetylcholine on isolated guinea-pig ileum were antagonized by esaprazole only at high concentrations. The present results suggest that the inhibitory actions of esaprazole on secretory parameters involve the cholinergic parasympathetic pathway, probably through both direct and indirect mechanisms.