The purpose of this study was to determine if autonomic nerve interventions exerted quantitatively dissimilar effects on recovery properties of endocardium compared with epicardium. Effective refractory periods (ERP) were measured by the extrastimulus technique in the endocardium and epicardium of the canine left ventricular anterior wall. The basic train and premature stimuli were administered to the endocardium and overlying epicardium via different poles on the same multipolar needle electrode, using cathodal stimuli. Sympathetic augmentation produced via bilateral carotid arterial occlusion or electrical stimulation of right, left, and both sympathetic nerves shortened ERP. Bilateral sympathetic denervation prolonged ERP. The changes in ERP of the endocardium were no different than were changes in the ERP of overlying epicardium. In separate studies, electrical stimulation of the cervical vagi prolonged ERP similarly in epicardium and endocardium. Pacing at slower rates or physostigmine administration potentiated the ERP prolongation in endocardium similar to epicardium. Augmented sympathetic tone produced by carotid occlusion also potentiated prolongation of ERP by vagal stimulation. The percent change in endocardial sites was slightly but significantly less than in epicardial sites. ERP prolongation due to vagal stimulation was attenuated markedly after sympathectomy and abolished with both propranolol and atropine. We conclude that, in the normal anterior left ventricular myocardium of the dog, sympathetic augmentation shortens ERP in epicardial sites equivalent to that in the underlying endocardial sites, that vagal nerve stimulation prolongs ERP in epicardial sites equal to or slightly greater than in the underlying endocardial sites, and that vagal stimulation antagonizes background sympathetic activity. Circ Res 46: 100-110, 1980