The class Ic antiarrhythmic agent propafenone was studied by repeated electrophysiologic testing in 54 patients (43 male, aged 54 +/- 10 years, mean ejection fraction of 37.3 +/- 16.9%) with ventricular tachyarrhythmias. Forty patients (74%) had coronary artery disease. Programmed ventricular stimulation (S2, S2S3 during sinus rhythm and/or during S1S1 = 500, 430, 370, and 330 ms) off antiarrhythmic drugs induced sustained ventricular tachycardia, flutter, or fibrillation in all patients. After 450-900 mg of oral propafenone/day for 4-7 days, 51 patients were restudied. In the remaining three patients, spontaneous ventricular tachycardia occurred on drug therapy. Tachycardia induction was suppressed in 9 of 51 patients restudied (18%) and rendered more difficult to induce (basic stimulation drive greater-than-or-equal-to 40 beats/min higher than at control study) in another 7 patients (14%) (overall efficacy of 31%). The tachycardia rate decreased from 220 +/- 43 to 177 +/- 44 beats/min (p < 0.01). The right ventricular effective refractory period increased from 232 +/- 22 to 252 +/- 22 ms (p < 0.001). Responders to propafenone therapy had higher rates of inducible ventricular tachycardia at control (> 230 beats/min: 43%; less-than-or-equal-to 230 beats/min: 21%; p < 0.05), higher ejection fractions, and lower left ventricular end-diastolic pressures than nonresponders. Eleven of the 16 patients showing a positive response to propafenone therapy in electrophysiologic testing were discharged on propafenone alone. During follow-up (17 +/- 12 months), nine patients remained free from ventricular tachycardia, one patient had a relapse, and one patient died of noncardiac death. Thus, propafenone was acutely effective in 31% of patients undergoing repeated electrophysiologic testing. Eleven of 16 patients with positive response to drug testing were kept on long-term propafenone therapy. Propafenone was effective in 10 of these 11 patients (91%).