In the perfused stomach preparation of the anaesthetized rat the cholinergic agonists acetylcholine (ACh) and bethanechol stimulated gastric acid secretion. Both agonists produced similar maximal acid output (70 mumols/15 min) when infused intravenously. However, bethanechol was more potent, eliciting half maximal stimulation at 1.98 mumols/kg/h, while the corresponding dose of ACh was 10.95 mumols/kg/h. Secretory responses to either agonist were antagonized in a dose related fashion by blockade of muscarinic receptors with atropine. In contrast, inhibition of nicotinic receptors with hexamethonium produced a striking potentiation of ACh stimulated secretion whilst the bethanechol elicited secretion remained unaffected. In the presence of full nicotinic receptor blockade the ACh response curve was shifted to the left sixfold, half maximal stimulation being produced at 1.79 mumols/kg/h. Cimetidine partially inhibited the secretory responses elicited by either ACh or bethanechol while blockade of adrenoceptors (alpha and beta) did not affect acid output induced by cholinergic agonists. Secretion elicited by ACh is interpreted as being the composite effect of pro-secretory action and an inhibitory mechanism due to the activation of nicotinic receptors. Hexamethonium, through nicotinic receptor blockade, inhibits the restricting mechanism and thus reveals the full stimulatory action of ACh.