The tissue sensitivity to insulin and the metabolic clearance rate of insulin were evaluated in a new case of Werner's syndrome, by means of the euglycemic clamp technique using an artificial endocrine pancreas. The possible contribution of pancreatic insulin secretion and of reduced hepatic insulin breakdown to the peripheral hyperinsulinism was also studied by simultaneous determination of C-peptide and insulin levels and by analysis of the C-peptide/insulin molar ratio. The data obtained are consistent with the presence of marked insulin resistance and of reduced metabolic clearance rate of insulin in our patient, confirming what has been observed previously using other techniques. The finding of a reduced C-peptide to insulin ratio during the intravenous glucose tolerance test suggests that hepatic extraction of insulin could also be altered in Werner's syndrome, as found in several hyperinsulinism conditions, therefore contributing to peripheral hyperinsulinism.