In vitro and animal experiments suggest that a constitutional increase in vascular responsiveness to serotonin (5-HT) may play a role in the development of essential hypertension. We have studied the potential alterations in vascular responsiveness to the direct and catecholamine-potentiating effects of exogenous 5-HT in patients with essential hypertension, by comparing in vivo responsiveness of superficial hand veins to local infusions of 5-HT or to coinfusions of 5-HT and noradrenaline in unmedicated hypertensive patients and in healthy control subjects. The dorsal hand vein compliance technique was employed. There was no significant difference between patients and control subjects in the maximal 5-HT-induced venoconstriction or in the doses required for half-maximal venoconstriction (ED50) for 5-HT. Coinfusions of a constant dose of 5-HT caused a significant leftward shift in the dose response curve for noradrenaline as compared with noradrenaline alone. This was indicated by a 9.7 +/- 13.7 fold and a 10.4 +/- 13.8 fold increase in the ED50 for noradrenaline in the patient and control groups, respectively (p = 0.89 between study groups). Our results argue against a generalized increase in responsiveness to the direct or catecholamine-potentiating effect of 5-HT in vivo in vascular smooth muscle, associated with hypertension.