5-Hydroxytryptamine (serotonin) can evoke both contraction and relaxation of vascular smooth muscle. In disease, the constrictor component of the response to the monoamine appears to dominate. 5HT2-serotonergic antagonists favor dilatation, not only because they block the activating effect of serotonin on vascular smooth muscle, but also because they unmask the (endothelium-dependent) relaxation to the monoamine and brake the amplifying effect that it exerts on platelet aggregation. These properties of serotonergic antagonists help to explain their protective effects in vascular disease.