The function of the cardiac autonomic nervous system (ANS) was evaluated by comparison of normal subjects with cardiac transplant recipients. By use of standard intracardiac His bundle recording techniques, the following conclusions regarding basic cardiac electrophysiology were drawn: (1) the sinus node functions normally at rest despite autonomic denervation; (2) the AV node does not show the expected decrease in functional refractory period with increased heart rate in the denervated state, and (3) the adrenergic receptor of the cardiac conduction system does not depend upon autonomic innervation to function normally. Electro-physiologic studies of digitalis demonstrated: (1) in therapeutic doses, the AV nodal blocking effect of digitalis is autonomically mediated; (2) sinus node slowing by digitalis also requires an intact autonomic innervation. Arrhythmia analysis in 47 transplant patients revealed an increased incidence of ventricular arrhythmias in autonomic cardiac denervation. In addition, sudden death in the ischemic denervated heart does occur, weakening the concept of a primary role of the cardiac ANS in this phenomenon.