The endothelium releases a variety of factors which can affect vascular tone. Endothelium-derived relaxing factor or nitric oxide is a very potent vasodilator and inhibitor of platelet function. Its release has been demonstrated in a variety of human blood vessels. In most human vascular preparations, prostacyclin does not significantly contribute to the endothelium-dependènt relaxations. Prostacyclin is, however, an endothelium-derived product which can evoke vasodilation and inhibition of platelet aggregation. In addition, the endothelium of human veins can release endothelium-derived contracting factors produced by the cyclooxygenase pathway. Endothelin is an endothelium-derived vasoactive peptide which has profound vasoconstrictor properties in human arteries and particularly in veins. Its action can only be partially inhibited by calcium antagonists, while endothelium-derived nitric oxide and exogenous nitrovasodilators are effective antagonists of the peptide. The mechanisms and amounts of endothelin released in human blood vessels remains to be defined. Under physiological conditions, endothelium-derived relaxing factors appear to dominate. The release of endothelium-derived nitric oxide is reduced in atherosclerotic human arteries. This indicates that in cardiovascular disease endothelial dysfunction occurs; this may contribute in the pathogenesis of coronary artery disease, pulmonary hypertension and stroke. © 1990 Springer-Verlag New York, Inc.