Exposure to environmental tobacco smoke (ETS) has been linked to increased risk of lung cancer and cardiovascular diseases in nonsmokers. Current research suggests that some of these diseases are associated with elevated oxidative stress. We investigated the effect of antioxidant (AO) intervention on the lipid peroxidation biomarker F2-isoprostanes (F2-IsoPs), an index of oxidative stress, in plasma of nonsmokers exposed to ETS (passive smokers). We measured free F2-IsoP concentrations in plasma of 67 passive smokers at baseline and after 2 mo of daily intervention with AOs or placebo. The study subjects (47 females, 20 males; mean age 46 +/-15) were randomized into one of three treatment groups: vitamin C, "mixture" (vitamin C, vitamin E, and a-lipoic-acid), and placebo. Investigated confounders included plasma baseline AO levels, lipid and total cholesterol profiles, transferrin saturation, and C-reactive protein. Plasma F2IsoP concentrations of subjects in the vitamin C and mixture groups decreased significantly by 17.2 pmol/l (P = 0.0105) and 19.2 pmol/l (P = 0.0083) when compared with the placebo group (11.4% and 12.7%, respectively). Daily AO supplementation (especially with vitamin C) decreases this oxidative stress biomarker in passive smokers. This finding might be of importance for the prevention of ETS-associated adverse health effects in nonsmokers.