We investigated the effects of class III antiarrhythmic agents, d-sotalol, E-4031 and MS-551, on the currents of two cloned K channels, Kvl.2 (I_Kv1.2)and Kvl.4 (I_Kv1.4), by using the Xenopus oocyte expression system. Both I_Kv1.2 and I_Kv1.4 were sensitive to 4-aminopyridine and quinidine, but insensitive to tetraethylammonium, d-sotalol, E-4031 and MS-551. The results suggest that some types of structural proteins may be necessary for class III agents to inhibit the cardiac cloned K channels.