The acute effects of cryothermia on regional electrophysiology were examined in order to devise a means of localizing and monitoring the intramural progression of ventricular cryolesions during a two-minute period of cryothermia application. Intramural unipolar electrograms were recorded from multipoint plunge electrodes placed in the left ventricle in 15 dogs. Epicardial, intramural, and endocardial applications of cryothermia were then employed, and changes in the unipolar peak-to-peak amplitude (UPPA) of electrograms were recorded. The location and depth of the ultimate permanent cryolesion could be predicted by noting locations of those electrograms demonstrating a decrease in the UPPA to less than 30% of the control values. Such electrophysiological monitoring of the region of myocardium undergoing cryothermic ablation provides a means of limiting the ultimate cryolesion to the desired location and depth within the ventricular wall. This allows precise placement of cryolesions in specific areas of the left ventricle for the treatment of ventricular tachyarrhythmias by selectively ablating arrhythmogenic ventricular myocardium without inducing injury in surrounding nonarrhythmogenic myocardium. © 1983, The Society of Thoracic Surgeons. All rights reserved.