The use of cryosurgery near major coronary arteries for the treatment of supraventricular and ventricular tachyarrhythmias has caused concern over the possible deleterious acute and chronic effects of cryothermia on vessel patency and integrity. The present study was designed to examine both the acute and chronic effects of cryothermia on major coronary vessels in an experimental model that simulates clinical conditions. In the acute phase of the study, 10 dogs underwent direct cryothermic exposure of the left anterior descending (LAD) coronary artery while coronary artery flow and regional myocardial blood flow were calculated. Direct cryothermic exposure of the LAD resulted in total cessation of LAD blood flow 20 ± 4 seconds after institution of cryothermia. Arterial patency returned 29 ± 8 seconds after termination of cryothermic exposure. In the second phase of this study, 16 dogs had cryolesions applied directly over the LAD at myocardial temperatures of 37°C and during elective cardioplegic arrest at myocardial temperatures of 6 to 12°C. In addition, cryothermia was applied directly to the coronary sinus in these animals. The animals were allowed to live either 48 hours, 2 weeks, or 6 months after the initial procedure, and the cryolesions and underlying vessels were examined histologically. Although coronary arteriography at 6 months showed all coronary arteries to be patent, microscopic examination revealed coronary intimal hyperplasia to be present in the majority of the coronary arteries at the site of the cryolesion, particularly if the cryolesion had been applied during hypothermic, cardioplegic arrest. Cryothermia had no effect on the coronary sinus. This study provides evidence for cryothermia-induced coronary arterial damage that may produce hemodynamically significant coronary artery stenosis and suggests that caution be exercised when it is necessary to create cryolesions in the vicinity of major coronary arteries.