Cystic fibrosis (CF) is associated with chronic lung infection, inflammation, and elevated indices of oxidative stress. Recently, isoprostanes were shown to be a reliable in vivo marker of oxidant injury with 8-iso-PGF₂α, shown to cause airflow obstruction and plasma exudation in guinea pig lung. The present study was designed to examine the relationship between 8-iso-PGF₂α levels, plasma antioxidants, and clinical status in CF. We hypothesized that plasma 8-iso-PGF₂a levels would be higher in subjects with CF compared to healthy controls. Plasma 8-iso-PGF₂α levels were prospectively measured in 22 subjects with CF and nine healthy controls using an 8-isoprostane enzyme immunoassay kit along with plasma vitamins A, E, and β-carotene. Plasma 8-iso-PGF₂α levels were shown to be significantly elevated in the CF subjects compared to controls (319.6±52.6 vs. 145.0±21.0 pg/ml, P=0.005). Plasma levels of antioxidants were significantly lower for the CF subjects compared to the controls (vitamin A, P<0.003; vitamin E, P<0.001; and β-carotene, P<0.01). This study confirns significantly elevated lipid peroxidation in CF using 8-iso-PGF₂α levels.