Early afterdepolizations (EADs) induced by suppression of cardiac delayed rectifier I _Kr and/or I _Ks channels cause fatal ventricular tachyarrhythmias. In guinea pig ventricular myocytes, partial block of one of the channels with complete block of the other reproducibly induced EADs. Complete block of both I _Kr and I _Ks channels depolarized the take-off potential and reduced the amplitude of EADs, which in some cases were not clearly separated from the preceding action potentials. A selective L-type Ca²⁺ (I _Ca,L) channel blocker, nifedipine, effectively suppressed EADs at submicromolar concentrations. As examined with the action potential-clamp method, I _Ca,L channels mediated inward currents with a spike and dome shape during action potentials. I _Ca,L currents decayed mainly due to inactivation in phase 2 and deactivation in phase 3 repolarization. When EADs were induced by complete block of I _Kr channels with partial block of I _Ks channels, repolarization of the action potential prior to EAD take-off failed to increase I _K1 currents and thus failed to completely deactivate I _Ca,L channels, which reactivated and mediated inward currents during EADs. When both I _Kr and I _Ks channels were completely blocked, I _Ca,L channels were not deactivated and mediated sustained inward currents until the end of EADs. Under this condition, the recovery and reactivation of I _Ca,L channels were absent before EADs. Therefore, an essential mechanism underlying EADs caused by suppression of the delayed rectifiers is the failure to completely deactivate I _Ca,L channels.