Endothelial cells of the arterial wall can generate vasodilator and vasoconstrictor substances. The prototype of a vasodilator substance formed primarily in the endothelium is prostacyclin, although its main target under physiological conditions are the platelets. In addition, the endothelial cells respond to a variety of neurohumoral mediators by the liberation of an unidentified substance(s) (endothelium-derived relaxing factor) with a potent inhibitory effect on vascular smooth muscle, presumably because it accelerates the production of cyclic GMP in the latter. Endothelium-derived relaxing factor is very unstable, and has an extremely short half-life. It is inactivated by plasma proteins and thus does not fulfill a hormonal role. A metabolite of arachidonic acid may be involved in the production of endothelium-derived relaxing factor. Among the neurohumoral mediators which release it are: acetylcholine (through activation of muscarinic receptors), adenosine di- and triphosphate (P2-purinergic receptors), bradykinin, histamine (H1- or H2-histaminergic receptors, depending on the species), serotonin (S1-serotonergic receptors), substance P, oxytocin, thrombin and vasopressin (V1-vasopressinergic receptors). The release of the factor can also be triggered by aggregating platelets (because they release adenine nucleotides and serotonin) and by increases in shear stress. It is likely that endothelium-dependent dilatation helps to prevent intraluminal coagulation in arteries with a normal intima. Absence, or dysfunction of the endothelium may favor the occurrence of vasospasm. Endothelium-dependent relaxations are reduced in atherosclerotic blood vessels.(ABSTRACT TRUNCATED AT 250 WORDS)