Cardiotoxicity is an uncommon side-effect of 5-FU-based chemotherapy. Coronary artery vasospasms have been postulated to be involved in the pathogenesis of this rare but serious problem. We found high plasma levels of ET-1, a potent natural vasoconstrictor, in two patients who experienced two of the commonest clinical manifestations of 5-FU-induced cardiac toxicity--i.e., angina pectoris and chronic heart failure. We, therefore, propose ET-1 as the ultimate mediator of this toxicity, even though the mechanism of ET-1 increase in peripheral venous blood is still unknown. Finally, another important question still remains unresolved: is the release of ET-1 from normal coronary endothelial cells the prime cause or simply the consequence of 5-FU-related cardiotoxicity?