Electrophysiologic testing was performed in 31 patients with ventricular tachycardia (21 cases) and fibrillation (10 cases) to characterize the electrophysiologic properties of patients responding or not responding to therapy with class III antiarrhythmic drugs. At the baseline, there were no differences among the patients in the monomorphic VT cycle length (CL), block CL or the width of the zone of entrainment. Ventricular tachyarrhythmias after the administration of class III drugs (sotalol: 9, amiodarone: 15 and E-4031/MS-551: 7) were inducible (non-responders) in 17 patients and non-inducible (responders) in 14 (45%). The class III drugs prolonged the sinus cycle length (SCL), QT interval and right ventricular effective refractory period (VERP), but had little effect on ventricular conduction time in the responders and non-responders. The SCL, QT interval and VERP at the three drive cycle lengths of 600, 400 and 300 msec were significantly longer in the responders than in the non-responders, but the class III drug action on VERP showed a reverse use-dependency. Isoproterenol administered to the responder did not fully reverse the class III antiarrhythmic drug-induced prolongation of QT, QTc and VERP, which remained significantly prolonged compared to the baseline values. Furthermore, when the VERP after the administration of class III drugs were greater than 270, 250 and 240 msec at the three drive cycle lengths of 600, 400 and 300 msec, respectively, it was associated with the non-inducibility of VT/VF. Though the precise mechanism of the drug efficacy is not yet known, these observations help to clarify the ability of class III drugs to prevent the induction of ventricular tachyarrhythmia.