The electrophysiologic changes produced by the intravenous administration of 0.6 mg/kg of sotalol were studied in 12 patients aged 45 to 85 years (mean 68 years). Effects upon atrioventricular (AV) nodal conduction time (AH interval) and His-Purkinje conduction time (HV interval) were assessed at identical rates. The Wenckebach cycle length was determined by rapid atrial stimulation. Refractory periods before and after the drug were compared at the same cycle length. Retrograde conduction was studied, with special reference to reentry phenomena within the His-Purkinje system. Sinoatrial function was evaluated using sinus node recovery time and sinoatrial conduction time. The following changes were noted: (1) decrease in sinus rate, (2) prolongation of QT interval, (3) depression of AV nodal conduction (prolonged AH interval) and increase in effective and functional refractory periods of the AV node, (4) increase in relative refractory period of the His-Purkinje system with no associated change in HV interval, (5) prolongation of effective refractory period in the atrium and ventricle, and (6) increase in retrograde refractory period of specialized ventricular tissue and depressed conduction of premature ventricular responses. Reentry phenomena in the His-Purkinje system were not significantly affected by the drug. Thus certain of the electrophysiologic effects of sotalol in humans were found to be in favor of a class III antiarrhythmic mechanism of action. These results justify further studies to evaluate the usefulness of this drug as an antiarrhythmic agent.