The effects of long term treatment with oral amiodarone on retrograde conduction ( S2H2 interval) and refractoriness of the His-Purkinje system were studied in 11 patients using His bundle electrograms and the ventricular extrastimulus method. Ten patients had ventricular tachycardia and one supraventricular tachycardia. Electrophysiological studies were carried out before and after the patients had been taking their maintenance dose for a mean duration of 84 days. After amiodarone treatment the HV interval was prolonged in seven patients and unchanged in four. At comparable S1S2 intervals, the S2H2 intervals were longer after treatment with amiodarone in all patients than before. Similarly, the longest S2H2 intervals achieved after amiodarone were longer than the control values. Amiodarone significantly increased the relative, effective, and functional refractory periods of the His-Purkinje system. Thus amiodarone exerts important effects on the His-Purkinje system.