Using a whole-cell voltage-clamp technique, we identified two time- and voltage-dependent K+ currents: an early outward rectifier and a delayed outward rectifier in single vascular smooth muscle cells of rabbit aorta in culture. About 90% of the single cells tested showed a predominant delayed outward K+ current type. Both K+ currents were decreased by tetraethylammonium. In contrast, bethanidine sulphate (10(-4)M), a pharmacological analog of the cardiac antifibrillatory drug, bretylium tosylate, decreased the early outward K+ current, increased the delayed rectifier K+ current type, and hyperpolarized the resting membrane potential. Bethanidine was found to relax vascular smooth muscle. The vasodilatory effect of bethanidine is associated with the activation of a K+ current that is probably involved in keeping the membrane potential at the resting state, thereby depressing the excitability of the aortic vascular smooth muscle.