In 16 patients undergoing elective coronary artery bypass, transmural biopsies were performed during bypass but before global ischemia. Subendocardial and subepicardial halves were separately assayed in each sampled tissue. Adenosine triphosphate (ATP) levels, total adenine nucleotide content (sigma Ad), and creatine phosphate (CP) content were significantly higher (p less than 0.005) in the subepicardium than the subendocardium in regions of the heart distal to major occlusions: 35.36 +/- 2.12 nmole/mg versus 28.7 +/- 1.7 (ATP), 42.24 +/- 2.04 versus 35.6 +/- 1.6 (sigma Ad), and 29.99 +/- 4.32 +/- versus 16.35 +/- 3.48 (CP). The opposite was true in two hearts with normal coronary arteries, in which high-energy phosphates tended to be higher in the subendocardium than the subepicardium. A transmural metabolic gradient therefore exists in regions of the myocardium distal to significant coronary occlusive disease. The subendocardium's relative depression in metabolic reserve cold determine its susceptibility to ischemic damage and influence techniques designed to preserve the heart during ischemia.