We have evaluated the metabolic clearance rate (MCR) of insulin and insulin sensitivity in 12 older patients with cystic fibrosis (CF) using the hyperinsulinemic euglycemic clamp method. Compared with a control group matched accurately for age and body mass index (BMI), the MCR of insulin was significantly enhanced in CF (CF = 21.85 ± 1.17 v controls = 16.01 ± 0.92 mL/kg/min, P < .005), and this difference persisted after correction for lean body mass ([LBM] CF = 26.32 ± 1.28 v controls = 19.09 ± 1.09 mL/kg LBM/min, P < .005). Glucose disposal rates (M) were similar in the two groups during the clamp (CF = 7.28 ± 0.41 v controls = 6.83 ± 0.60 mg/kg/min, P > .5), but the insulin sensitivity index, M I × 100 (I = steady-state insulin concentration), was markedly increased in the CF group (CF = 17.62 ± 1.30 v controls = 11.75 ± 0.71, P < .005). In conclusion, the MCR of insulin is enhanced in CF, which is in keeping with previous observations on drug metabolism in this disorder. Second, insulin sensitivity is increased in CF, and this points to a compensatory mechanism to counteract the insulinopenia. © 1994.