The mechanism of endothelin (ET) action on isolated myocytes of rat heart was investigated. Administration of 10(-9)-10(-7) mol/L ET caused dose-dependently severe contracture of myocytes, increase in cytosolic lactate dehydrogenase leakage and increase of cellular total calcium. ET also enhanced 45Ca2+ influx in myocytes, that could be antagonized by calcium channel blocker verapamil. Incubation of Fura-2 -preloaded myocytes with ET would induce a significant increase of cytosolic free Ca2+, and this effect of ET could also be partly antagonized by verapamil. These results suggest that ET enhances Ca2+ influx in myocytes mainly through voltage-dependent calcium channel, by which ET exerts its biological action.