Sensitivity to insulin in vivo was studied in 8 normal weight C-peptide negative Type 1 (insulin-dependent) diabetic patients (age 23 +/- 1 years, diabetes duration 6 +/- 2 years), and in 8 age, weight and sex matched healthy subjects, using the euglycaemic clamp and 3-3H-glucose tracer technique. Prior to the study diabetic patients were maintained normoglycaemic overnight by a glucose controlled insulin infusion. Sequential infusions of insulin in 3 periods of 2 h resulted in mean steady state insulin levels of 12 +/- 2 versus 11 +/- 1, 18 +/- 2 versus 18 +/- 2 and 28 +/- 3 versus 24 +/- 2 microU/ml in diabetic patients and control subjects. Corresponding glucose utilization rates were 2.4 +/- 0.2 versus 2.4 +/- 0.1, 2.4 +/- 0.2 versus 3.0 +/- 0.3 and 2.9 +/- 0.3 versus 4.6 +/- 0.6 mg.kg-1.min-1, p less than 0.02. Portal insulin values in the three periods were calculated to 12 +/- 2 versus 25 +/- 3, 18 +/- 2 versus 32 +/- 3 and 28 +/- 3 versus 37 +/- 3 microU/ml in the diabetic patients and control subjects using peripheral insulin and C-peptide concentrations and assuming a portal to peripheral insulin concentration gradient of 1 in diabetic patients and of 2.4 in control subjects. Corresponding glucose production rates were 2.5 +/- 0.2 versus 2.4 +/- 0.1, 1.6 +/- 0.1 versus 0.9 +/- 0.2 and 0.7 +/- 0.1 versus 0.4 +/- 0.2 mg.kg-1.min-1.(ABSTRACT TRUNCATED AT 250 WORDS)