Ventricular tachycardia commonly arises within the intraventricular septum and successful catheter ablation of septal tachycardia might be enhanced by transseptal electrode placement. We have evaluated the safety of a transseptal ablation procedure. Arrhythmogenicity and histology were examined after high-energy capacitor discharges were delivered to an intracavitary cathode-anode pair placed on opposite sides of the interventricular septum in pentobarbital-anesthetized dogs. After two discharges of 200 or 100 J proved lethal, paired discharges of 30 or 50 J (10 dogs) or a single discharge of 100 J (four dogs) was used to induce 28 lesions. Acute rhythm changes and risk of induction of ventricular tachycardia by programmed stimulation were measures of arrhythmogenicity. Gross and histologic examination of the hearts after 20 min to 28 days allowed characterization of the evolution of lesions. The conduction system in nearby and remote locations was extensively examined in four dogs. Refractory ventricular fibrillation developed with paired shocks at 200 or 100 J. At lower energy levels, acute ventricular fibrillation occurred with 12 of 20 shocks (60%), but defibrillation was consistently achieved. After ablation, no dog had ventricular tachycardia or fibrillation induced with programmed stimulation. Matching anodal and cathodal lesions spanned the septum without perforation in 10 of 16 dogs, and the lesions were of similar histology. Each contained central areas of hemorrhage surrounded by a region of coagulation necrosis merging with normal myocytes peripherally. There was necrosis and edema without inflammation at 20 min, acute inflammatory cell infiltration at 1 to 2 days, and myocyte replacement by granulation tissue after 6 days. Right ventricular apical perforation occurred near the septum without tamponade in one dog after a single 100 J discharge. There was no damage to the atrioventricular node, His bundle, or bundle branches in four dogs. We conclude that low-energy, paired-capacitor discharges can be safely applied through catheter electrodes that straddle the ventricular septum. Permanent cathodal and anodal injury results, without structural damage to the proximal conduction system. Circulation 74, No. 3, 637-644, 1986. LEFT SEPTAL endocardial resection has been used for control of arrhythmias in patients with ventricular tachycardia arising from the ventricular septum. 1-3 For those patients with an intramural septal location of the ventricular tachycardia focus, a more extensive ablative procedure might be required for optimal results. We reasoned that successful localization and ablation might be enhanced if tissue mediating the tachycardia were straddled by electrodes on both sides of the septum. To test the safety of this approach, a study was performed to determine lesion inorphology, degree of transseptal injury, and risk of