Endothelin is a potent and long-acting vasoconstrictor first isolated from the vascular endothelium. It was found in the search for the long-postulated endothelial vascular smooth muscle activator. Recent reports, however, suggest that endothelin may affect the release of the pituitary hormones and control the levels of atrial natriuretic peptide, renin, and the catecholamines. Its widespread distribution within the CNS and other tissues suggests that endothelin may have an important function as a neurotransmitter.