Sensitivity to insulin in vivo was studied in six Type 1 diabetic patients without residual insulin secretion and without clinical insulin resistance, and in eight non-diabetic subjects, using the euglycaemic insulin clamp technique. Insulin was infused for four periods of 2 h sequentially at 0.5, 1.0, 2.0 and 5.0 mU X kg-1 X min-1; for each insulin infusion period the steady-state plasma free insulin levels were comparable in the diabetic and non-diabetic subjects. The mean +/- SEM plasma glucose concentration was 4.9 +/- 0.03 mmol/l in the diabetic subjects (coefficient of variation of plasma glucose values: 5.7 +/- 0.7%) and 4.6 +/- 0.01 mmol/l in the control subjects (coefficient of variation: 5.1 +/- 0.6%). Insulin-mediated glucose disposal was lower in the diabetic than in the non-diabetic subjects at the two lower insulin infusion rates (mean +/- SEM = 2.03 +/- 0.27 versus 4.8 +/- 0.64 mg X kg-1 X min-1 at the first insulin infusion rate, p less than 0.01, and 5.59 +/- 0.59 versus 8.36 +/- 0.61 mg X kg-1 X min-1 at the second insulin infusion rate, p less than 0.01). However, insulin-induced glucose uptake did not differ significantly between the two groups at the third and fourth rates of insulin infusion. These results show that impaired insulin sensitivity in Type 1 diabetes is dependent on insulin concentration.