Epicardial mapping technics were used to locate the origin of ventricular ectopic beats produced by pacing and by the administration of ouabain and acetylstrophanthidin in pentobarbital-anesthetized open-chest dogs. The sequence of epicardial depolarization was determined with close bipolar reference and roving electrodes. The wave of excitation spread in concentric manner from driven points with the origin having the earliest time. Nonparasystolic unifocal ventricular tachycardia (UVT) was then aroused in nine dogs with ouabain or acetylstrophanthidin. Plunge electrodes were inserted for recording and stimulating of bundle of His and Purkinje fibers. Earliest epicardial ventricular activation of the UVT beats always occurred at or near the apex of the left ventricle. Purkinje fiber (PF) spikes from the region of earliest epicardial depolarization appeared just prior to ventricular activation. Pacing at this point produced QRS configuration almost identical to that during UVT. His bundle pacing normalized QRS configuration and suppressed UVT. Isolated right ventricular and left ventricular PF were perfused in the same tissue bath for microelectrode impalement. Infusion of ouabain increased the rate of automatic discharge of left ventricular PF before those from the right ventricle in each of five preparations. These studies suggest that digitalis-induced unifocal ventricular tachycardia originates below the His bundle from Purkinje tissue supplying the left ventricle and demonstrate that automaticity of canine PF from the left ventricle is preferentially enhanced by ouabain.