Electrical activation-guided laser photocoagulation was used intraoperatively to terminate ventricular tachycardia in patients with ischemic heart disease. During ventricular tachycardia, laser irradiation was delivered to mapped sites with local diastolic activation. In 30 long-term survivors, 85 ventricular tachycardia configurations were terminated by ablation; 72 (84.7%) were terminated by endocardial photocoagulation. Thirteen (15.3%) required epicardial photocoagulation; however, these 13 ventricular tachycardias occurred in 10 (33%) of the 30 patients. An aneurysm was present in 70% of patients with successful endocardial photocoagulation, but in only 10% of patients requiring epicardial photocoagulation for at least one ventricular tachycardia configuration; 90% of all patients requiring epicardial laser photocoagulation had no aneurysm and had either a right or a left circumflex coronary artery-related infarction. In this group, epicardial activation data were similar to those described for ventricular tachycardia with an "endocardial" origin and included 1) delayed potentials during sinus rhythm, 2) presystolic or pandiastolic activation sequences during ventricular tachycardia, and 3) regions of block near the presumed region of reentry during ventricular tachycardia. This study suggests that the critical anatomic substrates supporting reentry in postinfarction ventricular tachycardia may occur at intramural or epicardial sites, particularly in patients with right or circumflex coronary artery-related infarction and no aneurysm.