In 12 members of a family with MODY, insulin and C-peptide release after intake of a test breakfast was measured as well as binding of insulin to its erythrocyte receptor. According to serum glucose concentrations, subjects were classified into: diabetic, carbohydrate intolerant, and normal subjects. The two diabetic patients had an insulin release pattern similar to that of non-insulin dependent diabetics. The two patients with carbohydrate intolerance presented hyperinsulinism either at base state and after stimulation. Of the eight normal subjects, three presented high concentrations of serum insulin either at base level and after stimulation; in the remaining five, base insulinemia was normal and the response after food intake was poor. Insulin binding to the receptor was decreased in diabetic patients and this anomaly was more evident in patients with carbohydrate intolerance. In the three patients with increased serum insulin concentration, no disturbances in insulin-receptor binding were detected; in the remaining five patients, insulin-receptor binding was significantly decreased. Our findings prove that these subjects present a disturbance of insulin release and an impairment of insulin-receptor binding with a predominance of one or the other alteration even before hyperglycemia is evident.