Exaggerated insulin response to oral glucose was demonstrated in peripheral blood of patients with chronic hepatic diseases. High peripheral insulin levels may be the result of pancreatic hypersecretion or decreased hepatic removal of insulin. The simultaneous assay of insulin and C-Peptide concentrations in peripheral blood enables the determination of both beta-cell activity and hepatic fractional insulin extraction. We have measured peripheral insulin and C-Peptide levels during OGTT in a group of subjects with chronic active hepatitis (CAH). These subjects showed glucose levels and incremental areas significantly higher than controls, but still in the upper range of normality. Insulin response to oral glucose was significantly greater in CAH patients than in controls, whereas C-Peptide levels and areas were quite similar in the two groups. The C-Peptide to insulin molar ratios before and after glucose, and the relations between C-Peptide and insulin incremental areas were lower in CAH patients than in controls. We conclude that the peripheral hyperinsulinemia observed in subjects with CAH is due to diminished insulin removal by the diseased liver rather than pancreatic hypersecretion.