Myocardial blood flow has been recognized to be heterogeneous in patients with coronary artery disease. Traditional arterial-coronary sinus sampling methods cannot demonstrate comparable heterogeneity of myocardial metabolism. In this study we used a tracer technique to investigate possible heterogeneity of myocardial lactate metabolism. Twenty-one patients with symptoms of ischemic heart disease were studied. We injected14C-I-lactate intravenously as a constant infusion after a priming dose. Coronary sinus and arterial samples were obtained for chemical and radioisotopic analyses. At rest, myocardial lactate extraction by chemical analysis was 24.6 ± 8.5% (mean ± SD). By radioisotopic analysis, the lactate extraction was 41.0 ± 10.2% (p< 0.001). Thus, certain areas of the myocardium were releasing lactate despite global net extraction of lactate. In the 12 patients with significant left main or both left anterior descending (LAD) and left circumflex (LCX) lesions, the calculated amount of lactate released at rest was 0.136 ± 0.045, umol/ml of blood (mean ± SD). In contrast, the amount released in the six patients with a significant lesion in only the LAD or LCX was 0.076 ± 0.019 μmol/ml, and in the three patients without left coronary arterial lesions it was 0.039 ± 0.004 μmol/ml.Using a tracer method, myocardial lactate metabolism was demonstrated to be heterogeneous at rest in patients with ischemic heart disease. A significant amount of lactate can be released by the myocardium at a time when chemical arterial-coronary sinus analysis indicates global myocardial extraction. The amount of lactate released appears to be related to the severity of the coronary artery disease.