Strong immunoreactivity for endothelins (ETs) was observed in the endothelium of both human epicardial coronary arteries and veins. The contractile responses to ET-1, ET-2, and ET-3 were investigated in isolated circular human coronary vessel segments. ET-1, ET-2, and ET-3 induced significantly higher maximum contraction (measured in percentage of contraction induced by 60 mM potassium) and more potent responses in veins as compared with arteries. ET-1 as compared with ET-2 induced equal maximum contraction and equipotent responses both when tested in arteries and veins, whereas ET-3 induced lower maximum contraction and less potent responses in both vessel types. FR 139317, a selective ETA receptor antagonist, significantly decreased the potency of ET-1 and ET-2 responses in both human coronary arteries and veins, but the maximum effect obtained did not change significantly. The existence of ET immunoreactivity (IR) in endothelial cells from both human coronary arteries and veins indicates that ETs may be released endogenously. The effect of the selective ETA receptor antagonist FR 139317 indicates that the contraction induced by ET-1 and ET-2 in both arteries and veins is mediated by ETA receptors.