Myocardial exchange of metabolic substrates was investigated in eight Type 1 diabetic patients with angiographically normal coronary arteries and seven normal control subjects, after an overnight fast. Simultaneous samples of arterial and coronary sinus blood were collected for analysis of the major metabolic substrates. Myocardial blood flow was measured by the thermodilution technique. Although the Type 1 patients were hyperglycaemic (10.0 +/- 2.0 (+/- SE) mmol I-1) myocardial glucose uptake was lower than in control subjects (27 +/- 6 vs 42 +/- 5 mumol min-1 1.73 m-2, p less than 0.05). The net balance of lactate and pyruvate across the myocardium showed a net release in Type 1 patients (13.4 +/- 2.7 mumol min-1 1.73 m-2 and 1.3 +/- 0.2 mumol min-1 1.73 m-2, respectively) and a net uptake in control subjects (2.2 +/- 0.7 mumol min-1 1.73 m-2 and 3.5 +/- 0.3 mumol min-1 1.73 m-2, both p less than 0.01). Myocardial uptake of ketone bodies was significantly higher in diabetic patients (37.0 +/- 6.3) mumol min-1 1.73 m-2) than in control subjects (10.1 +/- 3.4 mumol min-1 1.73 m-2, p less than 0.01). Non-esterified fatty acid (NEFA) uptake was significantly greater in the diabetic patients than in control subjects (44.1 +/- 7.0) vs 24.1 +/- 5.1 mumol min-1 1.73 m-2, p less than 0.01). Net balance of glucose, lactate, and pyruvate across the myocardium was inversely and significantly related to that of NEFAs and ketone bodies (p less than 0.01). Myocardial carbohydrate uptake is markedly impaired in Type 1 diabetic patients with angiographically intact coronary vessels. Ketones and NEFA represent the major fuel for the diabetic myocardium. Thus, in diabetes, myocardial lactate metabolism may be profoundly altered independently of coronary artery disease.