In order to examine possible differences in mechanisms of action of nifedipine and verapamil, simultaneous recordings of membrane potential and cell motion were made during exposure of cultured chick embryo ventricular cells to these drugs. Both verapamil and nifedipine produced a rapid negative inotropic effect and excitation-contraction coupling delay presumably related to the ability of both agents to inhibit Ca2+ influx via the slow Ca channel, and thus decrease the [Ca2+]i transient. However, for an equivalent negative inotropic effect, verapamil produced relatively more membrane diastolic depolarization and slowing of repolarization than did nifedipine. Verapamil also produced a more marked decrease in +dV/dtmax. In ion flux studies, it was demonstrated that verapamil produced a significant inhibition of 24Na influx, relative to control, whereas nifedipine did not. Verapamil also produced a slight decrease in 42K efflux, of borderline significance. These findings support previous results which indicate there are differences in the mechanisms of action of these Ca2+-channel blocking drugs.