A potent endothelium-derived vasoconstrictive peptide, endothelin (ET), is processed from a precursor, big endothelin, by an unknown converting enzyme. It stimulates calcium channels, phospholipase C and phospholipase A2 in smooth muscle cells through activation of the receptor specific for ET. The intracellular free calcium ion concentration is increased by ET, inducing vasoconstriction. The response to ET varies according to the type of blood vessel. Mesenteric small arteries and arterioles are sensitive to ET. It is likely that various factors, including adrenaline, angiotensin II and arginine vasopressin, induce synthesis and release of ET from the endothelium. A balance among ET, endothelium-derived relaxing factor (EDRF) and atrial natriuretic peptide (ANP) may control vascular tone and regulate peripheral blood flow.