Despite the abundance of reports concerning the increased frequency of diabetes and impaired glucose tolerance in chronic liver diseases, the mechanisms underlying this phenomenon have not been resolved. 30 patients with hepatitis C virus (HCV) infection and 17 with hepatitis B virus (HBV) infection who showed an altered responds to a standard oral glucose tolerance test were investigated in order to evaluate their pancreatic-endocrine features. We have also evaluated 40 patients (20 with HCV infection and 20 with HCB infection) who developed diabetes after diagnosis of liver disease. Patients with HBV infection showed signs of enhanced insulin resistance but overt diabetes develops in those who, in addition to insulin insensitivity, have a relative defect of insulin secretion. In patients with HCV infection the significantly lower plasma insulin and C-peptide levels suggest that impairment of insulin secretion is the main mechanism leading to both glucose intolerance and overt diabetes.