Encainide is a newly developed antiarrhythmic agent. With the use of intracardiac electrophysiologic techniques, its effects on the cardiac conduction system were examined in 10 patients with coronary artery disease. Five patients received 0.6 and five received 0.9 mg/kg body weight of encainide intravenously over 15 minutes. Plasma concentration, heart rate, blood pressure and conduction intervals (A-H, H-V, QRS and Q-T) were measured before, during and after encainide infusion. In addition, sinus nodal recovery time, Wenckebach cycle length, and atrial, atrioventricular (A-V) nodal and right ventricular refractory periods were measured before and after encainide infusion. The average peak plasma concentration was 0.49 +/- 0.35 microgram/ml (mean +/- standard error of the mean). Encainide significantly prologned H-V and QRS intervals in all patients by an average of 31 +/- 7 and 18 +/- 9 percent (standard deviation) (P less than 0.001), respectively. A minimal increase in the Q-T interval was also observed after encainide infusion (2 +/- 9 percent, P less than 0.01), but no significant changes were noted in heart rate, blood pressure, A-H interval, corrected sinus noal recovery time, Wenckebach cycle length or refractory periods of the atrium, A-V node or right ventricle. It is concluded that encainide significantly prolongs conduction in the His-Purkinje system without affecting conduction or refractoriness of other parts of the cardiac conduction system in man.