We studied the effects of sevoflurane on contraction and membrane potentials in isolated canine ventricular muscle strips. Sevoflurane (> 0.5%) depressed electrically induced contraction in a dose-dependent manner. Moreover, sevoflurane did not show stimulation frequency-dependent depression in contraction as shown with local anesthetics. The inhibitory effect was more pronounced in high-K+ Tyrode's solution than in normal Tyrode's solution, suggesting that sevoflurane may inhibit transmembrane Ca2+ influx. In contrast, isoflurane and halothane were equally effective in depressing electrically induced contractions in normal and high-K+ Tyrode's solution. In electrophysiologic experiments, sevoflurane at higher concentrations (> 2.0%) depressed both overshoot and the plateau phase of the action potentials. These depressant effects were more pronounced in high-K+ Tyrode's solution. Resting membrane potential was not affected by sevoflurane. We conclude that depression of myocardial contractility by sevoflurane may be due to a block of the transmembrane calcium influx.