The effects of digoxin on sinus node and atrioventricular (AV) node function were studied in 18 patients (mean age 53.6 years) with normal intrinsic heart rates. Electrophysiologic testing was performed both during basal state and after autonomic blockade with propranolol and atropine. Full digitalization was achieved by intravenous administration of digoxin (0.02 mg/kg) given in three divided doses over a 24-hour period. The following day, after a basal recording, autonomic blockade was again induced and the study was repeated. During basal state, digoxin significantly prolonged the sinus cycle length (SCL) (p less than 0.01) and the AH interval (p less than 0.01). However, when the intrinsic sinus node functions were compared (i.e., the values obtained after autonomic blockade), digoxin did not produce significant changes in intrinsic SCL, corrected sinus node recovery time, and sinoatrial conduction time. No significant changes were noted even in the intrinsic AH interval and AV nodal refractory periods. These findings suggest that: (1) intravenous administration of digoxin in therapeutic doses does not produce any depression of the intrinsic functions of the sinus node and AV node; and (2) the depressant effects induced by digoxin during basal state appear to be mediated through the autonomic nervous system.