Increased free radical production has been suggested as a possible mechanism involved in lung deterioration of patients with cystic fibrosis (CF). Vitamins A and E are known to be involved in the defense mechanism preventing damage caused by free radicals. Both vitamins are fat-soluble and are therefore malabsorbed in patients with CF. We hypothesized that low concentrations of vitamins A and E may be involved in the increased free radical production of these patients. Neutrophils' chemiluminescence and superoxide and hydrogen peroxide production were examined in 11 patients with CF aged 4 to 14 years, and 10 age-matched healthy controls. All our patients were on prolonged supplementation with vitamins A and E, but the control group was not supplemented. Serum vitamins A and E levels and neutrophil vitamin E concentrations were examined concomitantly. Chemiluminescence production was increased 10 minutes after neutrophil stimulation by phorbol myristate acetate (PMA) as compared with that in normals (20,400 ± 9,463 v 11,990 ± 3,778 cpm, P < .03). No difference was found in superoxide or hydrogen peroxide production between CF patients and controls. Serum vitamin A levels were significantly higher in CF patients compared with healthy controls (0.641 ± 0.049 v 0.398 ± 0.038 mg/L, P < .04) and so were vitamin E levels (13.94 ± 2.25 v 5.64 ± 1.15 mg/L, P < .05). Neutrophil vitamin E concentrations were higher in CF patients compared with healthy controls ( 70.8 ± 26.0 v 23.6 ± 9.0 μg 106 cells). We conclude that neutrophils from CF patients exhibit increased chemiluminescence activity not related to increased free radical production or fat-soluble vitamin deficiency.