There are two types of non-prostanoid endothelium-derived vasoactive factors, one which relaxes and the other which contracts the vascular smooth muscle (EDRF and EDCF). These factors are released in response to stimulation of specific membrane receptors of the vascular endothelium by a large number of agonist substances and in response to physical stimuli to the vascular wall. It has been shown that EDRF is nitric oxide (NO) and EDCF has recently been identified as a peptide composed of 21 amino acids called endothelin. Other compounds may also act as EDRF or EDCF. EDRF (NO) induces relaxation of the underlying vascular smooth muscle by increasing intracellular concentration of cyclic guanosine monophosphate. The mechanisms of action of endothelin have not yet been clearly defined. It would seem that they depend, at least partially, on influx of extracellular calcium. The recent discovery of endothelin and the increased knowledge of the mode of action of EDRF on vascular smooth muscle has led to the suggestion that, vasomotor tone in humans is probably the result of an equilibrium between these two factors, each of which play a fundamental role, and very likely interact with each other in maintaining and regulating vascular tone in man.