Oxidation injury results in foam cell formation, which is known to be a central mechanism in atherogenesis. We investigated in this study whether 8-epi-prostaglandin (PG) F2 alpha, an in vivo indicator of oxidative stress, is elevated in hyperlipoproteinemia. The isoprostane 8-epi-PGF2 alpha levels in plasma, serum and urine were determined in 123 patients (67 m, 56 f; 17-60 years) suffering from familial heterozygous hypercholesterolemia (FH). A group of 99 normocholesterolemic adults (51 m, 48 f; 20-63 years) served as controls. Plasma, serum and urine levels of 8-epi-PGF2 alpha were significantly (p < 0.01) higher in the FH group. Smokers showed elevated 8-epi-PGF2 alpha levels; however, no correlation was observed to hypertension, age and sex. Successful dietary and drug treatment of FH patients resulted in a significant decrease in 8-epi-PGF2 alpha levels in plasma, serum and urine. These findings indicate that FH is associated with increased oxidation injury, which is beneficially influenced by successful dietary and/or drug treatment.