Background.: Allograft coronary artery disease (CAD) is a major long-term complication in heart transplanted patients. However, the metabolic basis of allograft CAD remains to be fully elucidated. We analyzed the lactate dehydrogenase heart (H) and muscle (M) isoenzyme pattern in endomyocardial biopsy specimens and the evolution of the H/M ratio to test whether changes in this ratio could be the earliest manifestation of allograft CAD. Methods.: Twenty-four heart transplant recipients were followed up for 12 months. Endomyocardial biopsy was performed at 1, 2, 3, 6, and 12 months after transplantation. Lactate dehydrogenase 1 through 5 isoenzymes were separated by electrophoresis, and the H/M ratio was calculated. Two groups of patients were identified: group 1 (n = 20), patients without allograft CAD; and group 2 (n = 4), patients with poor outcome (three deaths, 1 case of low cardiac output) and angiographic and histologic evidence of allograft CAD. Results.: Both groups had similar H/M baseline values. The H/M ratio was higher (p = 0.01) in group 1 at 6 months (3.48 ± 0.64 versus 2.17 ± 0.43) and 12 months (3.76 ± 0.92 versus 2.18 ± 0.45) when compared with group 2. The H/M ratio increased from 2.78 ± 0.89 at 1 month to 3.76 ± 0.92 at 12 months (p = 0.02) in group 1 and decreased in group 2 (2.86 ± 0.49 versus 2.18 ± 0.45; not significant). Conclusions.: Changes in H/M ratio reflect an anaerobic shift in the lactate dehydrogenase isoenzyme composition and can be taken as an early indicator of allograft CAD.