The endothelium can profoundly affect vascular tone by releasing endothelium-derived relaxing and contracting factor. Nitric oxide (EDRF) is the most important relaxing factor that is released from L-arginine and evokes relaxation by increasing intracellular cyclic GMP in vascular smooth muscle. Endothelin and other endothelium-derived contracting factors (i.e., a cyclooxygenase product and a substance released during hypoxia) may be released as well. In hypertension and atherosclerosis, endothelium-dependent relaxations are impaired and endothelium-dependent contractions may occur, at least in some blood vessels. These changes in endothelium function may promote vasospasm and vascular occlusion and contribute to increased vascular resistance in hypertension. The more effective release of EDRF in arterial coronary bypass grafts-which have a better patency than venous grafts-is in line with the concept that EDRF may play a role in the prevention of vascular occlusion.