Thirteen dogs in whom at least one morphologically distinct sustained ventricular tachycardia (VT) could be reproducibly initiated by programmed cardiac stimulation 18 ± 3 days following experimental myocardial infarction were placed on total cardiopulmonary bypass for detailed study of the endocardial and epicardial activation during VT under hemodynamically stable conditions. Thirteen morphologically distinct monomorphic VTs were investigated by simultaneous epicardial, endocardial, and intramural bipolar recordings. Local electrograms were used to generate computer-assisted isochronous-activation sequence maps. A complete reentry circuit could be mapped on the epicardial surface in 4 animals and on the endocardial surface in one other animal. In the remaining 8 animals, there was a gap period lasting 43-62 msec in the cardiac cycle during which no endocardial or epicardial activity was observed. In 6 of the 8 animals, bipolar intramural recordings from sites closely associated with regions of endocardial and epicardial conduction block showed intramural activity progressing slowly during the gap period. In these 6 animals, a reentry circuit could be completed by incorporating the local electrograms recorded from the intramural sites. VT could be reproducibly terminated by selectively rendering only these intramural sites refractory by critically timed extra-stimuli that failed to result in global ventricular capture. VT could be terminated by epicardial cooling in 2 of the 4 animals with epicardial reentry. By contrast, epicardial cryoablation did not effect intramural reentry and failed to interrupt VT. In this study, intramural pathways constituted an integral part of the reentry circuit in a large proportion of the VTs.