Experiments were performed to determine the effect of ergonovine on adrenergic neurotransmission in the blood vessel wall. Strips of canine left circumflex coronary arteries and saphenous veins were incubated with [3H]norepinephrine and suspended for superfusion. Ergonovine (10(-6) M) decreased the overflow of [3H] norepinephrine to a modest degree in the coronary artery, whereas a profound inhibition of overflow was observed in the saphenous vein. Methiothepin, but not rauwolscine, reversed the inhibitory effect of ergonovine in both blood vessels. Treatment with atropine or droperidol did not alter the response to ergonovine in the coronary artery. The results demonstrate that ergonovine, by activating prejunctional serotonergic receptors, inhibits adrenergic neurotransmission to a greater extent in the saphenous vein than in the coronary artery. The differential effect of ergonovine on norepinephrine release in these vessels may provide evidence for heterogeneity in the prejunctional modulation of adrenergic neurotransmission.