Serotonin possesses both vasoconstrictor and vasodilator properties. The constrictor action of the monoamine can be due to: (a) direct activation of vascular smooth muscle; in most blood vessels, this is mediated by S2-serotonergic receptors; (b) augmentation (amplification) of the action of other endogenous vasoconstrictors such as catecholamines, angiotensin II and the prostanoids; and (c) release of norepinephrine from adrenergic nerves. The dilator action of serotonin can be due to: (a) activation of endothelial cells which release endothelium-derived relaxing factor(s); this response appears to be mediated by S1-serotonergic receptors; (b) direct inhibition of vascular smooth muscle; (c) inhibition of adrenergic neurotransmission by an action on S1-serotonergic prejunctional receptors; and (d) release of other endogenous mediators. The net effect of serotonin on the blood vessel wall depends on: (a) the integrity of the endothelium; (b) the degree of activation of the vascular smooth muscle; (c) the level of sympathetic tone; and (d) local (e.g. PO2, temperature) and chronic (e.g. blood pressure) modulating factors. S2-serotonergic antagonists prevent the constrictor action of serotonin, and often unmask its dilator potential.