The relationship of serum vitamin E, beta-carotene, vitamin C, and selenium to asthma was investigated among 7,505 youth (4-16 years old) in the Third National Health and Nutrition Examination Survey. Logistic regression models adjusted for potentially confounding variables, which generally had no effect on the coefficients for the antioxidants. Serum vitamin E had little or no association with asthma. In separate models, a SD increase in beta-carotene (odds ratio [OR], 0.9; 95% confidence interval [CI], 0.7, 1.0), vitamin C (OR, 0.8; 95% CI, 0.7, 0.9), and selenium (OR, 0.9; 95% CI, 0.7, 1.1) was associated with a 10-20% reduction in asthma prevalence. Serum cotinine was used to identify youth with no cigarette smoke exposure and passive exposure (7%): Active smokers were too few to be studied further. The selenium-asthma association was stronger in youth who were smoke exposed (p = 0.075). A SD increase in selenium was associated with a 50% reduction in asthma prevalence (OR, 0.5; 95% CI, 0.2, 1.4) in youth with passive smoke exposure compared with a 10% reduction in youth with no smoke exposure. The findings support an association of antioxidants with prevalent asthma, which for some antioxidants is stronger among children exposed to cigarette smoke.