Myocardial ischemia induced by aortic cross-clamping and hypothermic potassium cardioplegia were studied in normal mongrel dogs (group II), and in dogs with two types of surgically induced left ventricular hypertrophy. One hypertrophy group had chronically hypertensive coronary arteries secondary to ascending aortic banding (group III); the second group had surgically produced aortic valve stenosis, and consequently had normotensive coronary arteries (group IV). These three groups were compared to a control group of normothermic dogs (group I) with each animal being subjected to 60 minutes of ischemia followed by 30 minutes of reperfusion. In groups HI, III, and IV, the myocardium was cooled to 20°C at the onset of crossclamping, and recooled to 20°C every 15 minutes by perfusing with 4°C cardioplegic solution through the aortic root. Serial "stop freeze" left ventricular biopsies assayed for adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), and creatine phosphate (CP) revealed significant protection from depletion of high-energy phosphates in all three cardioplegic groups at the end of the ischemic period. The ATP concentrations in the group I animals dropped from 5.0 ± 0.3 to 1.8 ± 0.2 Aumoles/g during the cross-clamp period while the group II animals varied from 4.3 ± 0.4 to 5.1 ± 0.4, group III from 4.2 ± 0.6 to 4.3 ± 0.7, and group IV from 3.9 ± 0.6 to 5.4 ± 0.7 μmoles/g during the same period. During reperfusion, all of the cardioplegia-treated hearts displayed a "reperfusion injury" manifested by a significant (p < 0.05) drop in myocardial ATP concentrations. By the end of the 30-minute reperfusion period, groups II, III, and IV exhibited ATP levels of 3.3 ± 0.7, 3.6 ± 0.3, and 3.6 ± 0.8 μmoles/g, respectively. However, these ATP values were still significantly higher than the 2.1 ± 0.3,4moles/g of the control animals at the end of reperfusion. These data indicate that hypothermic potassium cardioplegia effectively attenuates metabolic injury resulting from 1 hour of global ischemia in the hypertrophic myocardium but does not prevent reperfusion injury.