Non prostanoid endothelium-derived relaxing and contracting factors (EDRF and EDCF, respectively) are released by endothelial cells and act on the underlying vascular smooth muscle. It is now established that EDRF is nitric oxide (NO), whereas EDCF has been recently identified as a 21 residue peptide, called endothelin. However, circumstantial evidence suggests that there may be more than one EDRF and/or EDCF. EDRF (NO) induces relaxation of the underlying vascular smooth muscle by enhancing intracellular level of cyclic guanosine monophosphate. The mechanisms of action of endothelin are still to be defined. It seems however that influx of extracellular calcium may partly account for its action. Although important findings have been made recently, most of the hypotheseses, at our current stage of knowledge, about the respective roles of EDRF and EDCF in disease have still to be proved. However, it is preferable from now to think in terms of balance (or imbalance) between these two factors which, probably, have both a fundamental role and very likely interact with each other in maintaining and regulating vascular tone in man.