Endothelial cells exert potent effects on vascular tone and platelet activity by the release of autacoids. One of the functionally most important autacoids is the endothelium-derived relaxant factor (EDRF). It inhibits platelet and vascular smooth muscle activation by cGMP-dependent attenuation of the agonist-induced rise of intracellular free Ca2+. Recent experiments suggest that EDRF has a physiologic role in the control of the vascular tone of large arteries and resistance vessels. Furthermore, there is evidence that an impairment of EDRF release may be a significant pathophysiologic factor in myocardial ischaemia. Coronary vascular tone might be also affected by the endothelium-derived vasoconstrictor peptide, endothelin, but its significance for the control of coronary blood flow remains to be elucidated.