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-PGF2 alpha, shown to cause airflow obstruction and plasma exudation in guinea pig lung. The present study was designed to examine the relationship between 8-iso-PGF2 alpha levels, plasma antioxidants, and clinical status in CF. We hypothesized that plasma 8-iso-PGF2 alpha levels would be higher in subjects with CF compared to healthy controls. Plasma 8-iso-PGF2 alpha 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 beta-carotene. Plasma 8-iso-PGF2 alpha 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 beta-carotene, P < 0.01). This study confirms significantly elevated lipid peroxidation in CF using 8-iso-PGF2 alpha levels.