Serotonin has complex effects on the cardiovascular system. In the intact animal it may cause increases or decreases of blood pressure and in isolated blood vessels contraction or relaxation depending on the species and vascular bed studied, the route of administration and the dosage used. Contractions evoked by the monoamine are mediated mainly by S2-serotonergic receptors on vascular smooth muscle; in addition, serotonin may act indirectly by amplifying the response to norepinephrine and other agonists, by displacing norepinephrine from adrenergic nerve terminals or releasing constrictor substance(s) from the endothelium. Dilatation in response to serotonin is mediated by endothelial and prejunctional S1-serotonergic receptors which pharmacologically resemble 5-HT1-binding sites. In hypertension, constrictor responses to serotonin are augmented, while the vasodilator effects of the monoamine are decreased. The constrictor response to serotonin is increased more than those to other agonists, suggesting a functional rather than a structural adaptation of the hypertensive blood vessel wall. In hypertension the turnover of circulating platelets, the major source of peripheral serotonin, is accelerated and the mechanisms for the removal of the monoamine are impaired. The functional changes of the blood vessel wall and platelets could play a role in the maintenance of the increased peripheral vascular resistance in chronic hypertension, and they could be involved in the pathogenesis of complications of the hypertensive process. The concept that serotonin plays a role in chronic hypertension is further supported by the antihypertensive properties of the S2-serotonergic antagonist, ketanserin.