Myocardial and skeletal muscle glucose uptake was examined in 9 type 2 diabetic patients and 13 control subjects using PET and the insulin clamp technique. All subjects had clinically stable coronary heart disease. To simulate the clinical situation, diabetic patients were kept slightly hyperglycemic during the clamp study. Consequently, there were no differences in skeletal muscle or total body glucose disposal between the two groups. With PET, myocardial glucose uptake was 12-20-fold greater than that in skeletal muscle in both groups. However, in the diabetic patients, myocardial glucose uptake was 39% lower (p < 0.05) than in the control subjects. These data suggest a defect in myocardial glucose utilization in type 2 diabetes and emphasize the need for standardized metabolic conditions in diabetic patients during 18FDG PET imaging.