To darify the cardiotoxic mechanism, the effect of bupivacaine on the cardiac function, especially in coronary flow rate was inveetigated in the isolated working rat heart. When administered into left atrium of the heart, lidocaine(10(-6)-10(-4) M) decreased heart rate in a dose-related fashion, whereae rate of coronary flow and mean coronary resistance tend to decrease and increase transiently, respectively. On the other hand, bupivacaine decreased the coronary flow rate and increased the mean coronary resistanee in a dose(10(-6)-10(-4) M) dependent manner. However, the decrement of heart rate by bupivacaine was not clear, but larger dose(10(-4) M) produced marked bradycardic effect. Bupivaeaine decreased the coronary flow and increased the mean coronary resistance in the isolated working heart, in which the heart rate and aortic pressure were kept constantly by electrical stimulation(3-6 pps, 0.5 mS, 20 V). These effects of bupivacaine were not influenced by 1 uM prazosin and 2 uM atropine pretreatment. But the bupivacaine effeets were completely abolished by 100 mM KC1 pretreatment and were inhibited markedly by 10(-7) M diltiazem, a Ca2+ -antagonist, pretreatment. From these results, it is suggested that the bupivacaine-induced coronary flow decrease is elicited via direct coronary vasoconstriction. And this vasoconstriction is due to the increments of intracellular Ca2+ concentration.