Experiments were designed to determine the mechanism by which electrical stimulation causes tetrodotoxin-insensitive relaxation in isolated arteries. Rings of left anterior descending coronary arteries of dogs, pigs and calves were suspended in organ chambers between platinum electrodes. Experiments were performed after treatment with phenoxybenzamine and in the presence of propranolol. Calcium-free solution and calcium antagonists reduced the relaxation. Chemical denervation with 6-hydroxydopamine reduced the relaxation induced by electrical stimulation; in the presence of pargyline, the inhibitor of monoamine oxidase, it was virtually abolished. The nonselective dopaminergic antagonist droperidol and the selective DA1-dopaminergic antagonist SKF R83566 caused a concentration-dependent inhibition of the relaxation; the DA2-dopaminergic antagonist domperidone was ineffective. High concentrations of dopamine induced relaxation of the coronary smooth muscle; the relaxation was inhibited by SKF R83566 but not by droperidol. These results suggest that electrical stimulation causes relaxation by liberating an endogenous vasodilator substance, which acts on DA1-dopaminergic receptors of the coronary smooth muscle.