Skeletal muscle insulin resistance and coronary heart disease (CHD) often precede non-insulin-dependent diabetes mellitus (NIDDM). A recent study showed the myocardium of patients with CHD to be insulin resistant, independent of blood flow. We determined whether myocardial insulin resistance is a feature of NIDDM patients with no CHD. Skeletal muscle and myocardial glucose uptake were determined in 10 patients with NIDDM and 9 age- and weight-matched normal men of similar age and body mass index men using [18F]-2-fluoro-2-deoxy-D-glucose and positron emission tomography under normoglycaemic hyperinsulinaemic conditions. Whole body glucose uptake, as determined by the euglycaemic clamp technique, was significantly lower in the patients with NIDDM (35+/-3 micromol/kg body weight min) than the normal subjects (45+/-3 micromol/kg body weight x min, p < 0.02). Insulin-stimulated femoral muscle glucose uptake was significantly lower in the patients with NIDDM (71+/-6 micromol/kg muscle x min) than in the normal subjects (96+/-5 micromol/kg muscle x min, p < 0.01). Whole body glucose uptake was correlated with femoral muscle glucose uptake in the entire group (r=0.76, p < 0.001), in patients with NIDDM and in normal subjects. Rates of insulin-stimulated myocardial glucose uptake were comparable between the patients with NIDDM (814+/-76 micromol/kg muscle min) and the normal subjects (731+/-63 micromol/kg muscle min, p > 0.4). Whole body or femoral muscle, and myocardial glucose uptake were not correlated in all subjects, patients with NIDDM or normal subjects. We conclude that insulin resistance of the myocardium is not a feature of uncomplicated NIDDM.