Plasma antioxidant status and total radical-trapping antioxidant potential (TRAP) of children (n = 24) with cystic fibrosis (CF) were compared with those of children (n = 21) without the disease. Children with CF were found to have elevated plasma concentrations of ascorbic acid (94.6 +/- 58.2 mumol/L), with respect to normal children (65.6 +/- 18.8 mumol/L). Plasma uric acid (330.8 +/- 84 versus 198.0 +/- 31 mumol/L p < 0.01) and sulfhydryl group (518 +/- 43 versus 363 +/- 31 mumol/L p < 0.01) concentrations were also elevated in CF. Vitamin E levels (16.9 +/- 1.8 versus 18.4 +/- 1.3 mumol/L) were at the low end of the normal range. Despite an overall increased antioxidant array, CF patients had a reduced TRAP capacity (488 +/- 34 versus 580 +/- 79 mumol/L, p < 0.05). TRAP measurements in CF patients showed a strong negative correlation (r = 0.80, p < 0.001) with high ascorbic acid concentration, suggesting a prooxidant effect of ascorbic acid. Oral administration of ascorbic acid to adults was found to diminish TRAP activity. Concentrations of ascorbic acid similar to those seen in CF patients were attained in ascorbate-supplemented individuals, with substantial decreases in TRAP capacity. These studies suggest that high plasma ascorbic acid levels in children with CF may have a prooxidant effect. This appears to reduce the extracellular antioxidant defense of these children and may increase susceptibility to oxidative stress.