Employing an isolated perfused rat heart preparation, we investigated the contribution of anaerobic metabolic energy to the performance, recoverability, and ultrastructure of the heart perfused at 32°C in 5% albumin in Krebs-Ringer Bicarbonate solution. During exposure to anoxia for 30 min, inclusion in the perfusate of the anaerobic substrate, glucose, resulted in marked improvement in electrical and mechanical performance of the heart and in enhanced recovery during the subsequent period of reoxygenation. Lactate production was fivefold greater in the glucose-supported anoxic heart than in the anoxic heart without glucose. Electron microscope sections of the hearts exposed to anoxia in the absence of glucose revealed alterations in mitochondrial morphology and dilatation of the longitudinal tubules. These morphologic changes during anoxia were averted by inclusion of glucose in the perfusion fluid. The data are consistent with the hypothesis that anaerobic energy generation plays a significant role in preserving myocardial function and structure and in promoting recoverability of the anoxic mammalian heart.