Evidence of lipid peroxidation previously documented in cystic fibrosis (CF) implies an imbalance between free radical generation and antioxidant defense mechanisms. The aim of the present study was to examine the relation between plasma concentrations of malondialdehyde, a marker of lipid peroxidation, and the exogenous antioxidant line of defense. Malondialdehyde concentrations (90.2 +/- 4.7 nmol/L) in 25 children with CF aged 9.6 +/- 0.8 y were higher (P < 0.001) than concentrations (69.1 +/- 2.6 nmol/L) in 17 children used as control subjects and were not correlated with any marker of disease severity. In contrast with their all-rac-alpha-tocopherol status, which was normal as a result of routine supplementation with a 200-mg dose of all-rac-alpha-tocopheryl acetate/d, beta-carotene was very low. A 2-mo open trial in which 12 children with CF aged 11.5 +/- 0.8 y were given 4.42 mg (8.23 mumol) beta-carotene three times per day led to normalization of the malondialdehyde concentration in all but 1 patient, in conjunction with an increase of plasma beta-carotene from 0.08 +/- 0.03 to 3.99 +/- 0.92 mumol/L. Their plasma concentrations were inversely correlated (r = -0.54, P = 0.006) [corrected] with malondialdehyde when the values measured pre- and posttreatment were pooled. We conclude that beta-carotene deficiency contributes to lipid peroxidation in CF and that supplementation may eventually prove to be a useful adjunct for the management of the disease.