To elucidate the mechanism of glucose intolerance in chronic liver disease (CLD), the kinetics of plasma glucose, insulin and C-peptide were studied after intravenous glucose loading in patients with CLD. Fasting plasma insulin levels were higher in patients with CLD than in normal subjects. This hyperinsulinemia was attributed primarily to an increased pancreatic secretion of insulin. Patients with CLD were divided into two groups, one with normal fasting plasma glucose (FBS less than 100 mg/dl (Group I) and the other with higher FBS (Group II). In Group I, the glucose disappearance rate was normal and a brisk acute insulin response (AIR) to glucose was noted. The glucose disappearance rate in Group II was lower than that in normal subjects, and AIR to glucose was blunted. It is suggested that normal glucose tolerance in Group I patients could be interpreted as a state of compensation by hypersecretion of insulin. On the other hand, the glucose intolerance in Group II patients could be due to inadequate insulin secretion to overcome insulin resistance of CLD.