1. Simplified protocols for the measurement of insulin resistance will facilitate studies of this potentially important variable. 2. Using the euglycaemic clamp as the reference technique, we have assessed the validity of the insulin sensitivity index (inversely related to insulin resistance) obtained using a high-dose (500 mg/kg), unmodified intravenous glucose tolerance test with a 16 point sampling schedule and analysis using the minimal model of glucose disappearance. The two methods were compared in 10 clinically normal subjects and five patients with severe heart failure secondary to coronary heart disease. 3. The insulin sensitivity index of the minimal model was compared with four clamp-derived measures. Correlation coefficients of 0.72-0.92 (P < 0.01-P < 0.001) were obtained between the two methods over a wide range of insulin sensitivity [model values 1.03-14.63 min-1/(pmol/l) x 10(-5)]. Patients with heart failure had the lowest measures of insulin sensitivity. 4. The high-dose, unmodified intravenous glucose tolerance test with minimal model analysis is a straightforward and economical clinical procedure and provides a valid measure of insulin sensitivity, in health and disease.