The effect of Ni2+ on E-C coupling events of the frog ventricular muscle were studied using a single sucrose gap voltage clamp technique. The results showed that Ni2+ increased the overshoot potential and depressed and prolonged the plateau of the action potential. Ni2+ also increased the dependence of the overshoot potential on [Na]0 from 18 to 58 mV per decade. In the presence of Ni2+, TTX blocked both the upstroke and the plateau of the action potential. The combination of TTX and Ni2+ suppressed the tension-voltage relation, the time-dependent outward currents and K+ efflux. While suppression of the tension-voltage relation by Ni2+ alone was reversed by increasing [Ca]0, the effects of Ni2+ plus TTX are not reversed by addition of Ca2+. The results suggest that Ni2+ may alter the action potential by slowing the inactivation of the Na+ current and blocking the inward Ca2+ current. Although the tension-suppressant effects of Ni2+ could be attributed to the inhibition of a slowly inactivating Ca2+ current, the effects of Ni2+ in the presence of TTX were less readily explained. Several possible mechanisms are considered which are all consistent with the hypothesis that development of tension in ventricular strips is mediated by both a Ca2+ current and a Ca2+ counter-transport system.