OBJECTIVE We determined the changes in insulin, intact proinsulin and 32-33 split proinsulin as markers of beta cell damage in assessing the state of carbohydrate intolerance in patients with cystic fibrosis. METHODS Measurements of insulin, proinsulin and 32-33 proinsulin concentrations in cystic fibrosis following oral glucose tolerance test (OGTT). METHODS Sixteen cystic fibrosis patients attending the chest outpatient clinic for follow-up, age range 14-42 years, and 14 healthy controls matched for age and body mass index. METHODS Insulin, intact proinsulin and 32-33 split proinsulin were measured immunoradiometrically at 0, 30, 60, 90 and 120 minutes after an OGTT. Glucose and HbA1 were also measured. RESULTS Cystic fibrosis patients were divided into two groups according to their OGTT results: those with diabetes mellitus or impaired glucose tolerance and those with normal glucose tolerance. Insulin concentrations and insulin/glucose ratios at 30 minutes were lower in both cystic fibrosis groups in comparison with the control. There was also a significant increase in the time to reach peak insulin levels in both cystic fibrosis groups. Fasting intact proinsulin concentrations and the proportion of proinsulin-like molecules were significantly higher in cystic fibrosis with diabetes mellitus or impaired glucose tolerance than in the control group, but not in the normal glucose tolerance cystic fibrosis group. There was no significant difference in the plasma concentrations of 32-33 split proinsulin amongst the three groups. CONCLUSIONS Abnormal beta cell function in cystic fibrosis patients was reflected initially in a diminished 30-minute insulin response to oral glucose. A significant rise in fasting intact proinsulin and the proportion of proinsulin-like molecules was seen only in cystic fibrosis patients who had progressed to impaired glucose tolerance or diabetes mellitus. Cystic fibrosis patients with normal glucose tolerance showed changes intermediate between the control and the other group.