Previously we reported the cholinergic M₂ muscarinic receptor-mediated inhibition of noradrenaline release from the rat stomach (K. Yokotani, Y. Osumi. J Pharmacol Exp Ther. 1993;264:54–60). In the present study, we investigated the role of K⁺ channels in oxotremorine (a muscarinic receptor agonist)-induced inhibition of noradrenaline release using isolated, vascularly perfused rat stomach. The gastric postganglionic sympathetic nerves were electrically stimulated twice at 2.5 Hz for 1 min and test reagents were added during the second stimulation. The electrically evoked release of noradrenaline was augmented by tetraethylammonium and 4-aminopyridine (non-selective K⁺ channel blockers) and also by charybdotoxin (a blocker of big conductance Ca²⁺-activated K⁺ channel). On the other hand, apamin (a selective blocker of small conductance Ca²⁺-activated K⁺ channels) and glibenclamide (an ATP-activated K⁺ channel blocker) had no effect on the evoked noradrenaline release. Oxotremorine-induced inhibition of noradrenaline release was attenuated by tetraethylammonium and 4-aminopyridine, while the inhibition was not influenced by charybdotoxin, apamin, and glibenclamide. These results suggest that tetraethylammonium- and 4-aminopyridine-sensitive K⁺ channels (probably voltage-activated K⁺ channels) are involved in the muscarinic receptor-mediated inhibition of noradrenaline release from the rat stomach.