To investigate the efficacy of long-term oral beta-carotene supplementation for optimizing the antioxidant status and pulmonary function in patients with cystic fibrosis (CF), 24 patients (aged 12. 8 +/- 6.3 years) were randomized to a CF supplementation or to a CF placebo group. As controls 14 healthy age-matched subjects (aged 14. 7 +/- 6.2 years) were studied. Patients of the CF supplementation group received 1 mg beta-carotene/kg body weight (BW)/day (maximally 50 mg beta-carotene/day) for the first 12 weeks; during the following 12 weeks, dosage was reduced to 10 mg beta-carotene/day. At study entry, plasma beta-carotene concentrations were significantly lower in CF patients than in controls (p<0.001). In the CF supplementation group, plasma beta-carotene concentrations were significantly increased (baseline: 0.08 +/- 0.04 micromol/l) at the end of high-dose treatment (12th week; 0.6 +/- 0.4 micromol/l; p<0.001), but decreased again during supplementation with 10 mg beta-carotene/day to 0.3 +/- 0.2 micromol/l at the end of the study (p<0.001). beta-Carotene supplementation did not affect plasma concentrations of other carotenoids and retinol, but an increase in plasma alpha- and gamma-tocopherol concentrations was noticed. During high-dose treatment, a significant decrease in TBA-MDA complexes and a correction of total antioxidative capacity was observed. During the treatment, pulmonary exacerbation could be corrected significantly (p<0.05). We conclude that CF patients can be efficiently supplemented with 1 mg beta-carotene/kg BW/day (maximally 50 mg beta-carotene/day) to achieve plasma concentrations of healthy control subjects and to minimize oxidative stress, improving the quality of life of CF patients.