The purpose of this study was first to provide further data on the role of the sympathetic nervous system in the pathogenesis of ventricular arrhythmias produced by digitalis administration and also to ascertain whether the left or right stellate ganglia had diverse effects on arrhythmogenesis. To do this, we subjected alpha-chloralose-anesthesized guinea pigs to either right, left, bilateral or sham stellectomy and then infused ouabain until death under constant ECG monitoring. Only guinea pigs with right stellectomy showed a significant change (i.e., increase) in Q-Tc interval when compared with sham-operated controls. The increased Q-Tc interval seen in the right stellectomized group did not change during ouabain infusion whereas it became significantly shorter in shams and in left and bilateral stellectomized pigs. The right stellectomized animals were sensitized to the toxic effects of ouabain whereas, conversely, left and bilateral stellectomized animals were protected. Cause of death also varied with left and bilateral stellectomized animals dying of cardiac asystole and right stellectomized animals of cardiac fibrillation. These anatomic ablation experiments 1) confirm the earlier concept based on pharmacological and neurophysiological work that the sympathetic nervous system plays an important role in the initiation of digitalis-induced arrhythmias; 2) make the point that the arrhythmic trigger works preponderantly through the left stellate; and 3) suggest that use of digitalis in patients with the long Q-T syndrome may put them at further risk of developing arrhythmias.