The obligatory role of the endothelium in relaxations of isolated coronary arteries to acetylcholine is explained by the release by endothelial cells of a labile vasodilator substance(s), endothelium-derived relaxing factor(s). Other neurohumoral mediators can evoke endothelium-dependent relaxations of coronary arteries. Of particular importance from the clinical point of view are thrombin, serotonin and adenine nucleotides. The latter are chiefly responsible for the endothelium-dependent relaxations evoked by aggregating platelets. The absence or the dysfunction of the endothelium may favour the occurrence of vasospasm.