Recent studies have linked air pollution to tens of thousands of premature cardiovascular deaths per year. The mechanisms of such associations remain unclear. In this study we examine the association between blood markers of cardiovascular risk and air pollution in a national sample of the U.S. population. Air pollution concentrations were merged to subjects in the Third National Health and Nutrition Examination Survey (NHANES III) in the United States, and the association with fibrinogen levels and counts of platelets and white blood cells were examined. The subjects in NHANES III are a representative sample of the U.S. population. Regressions controlled for age, race, sex, body mass index, current smoking, and number of cigarettes per day. The complex survey design was dealt with using mixed models with a random sampling site effect. In single-pollutant models, PM(10) (particulate matter with a mass median aerodynamic diameter less than 10 microm) was associated with all three outcomes (p< 0.05): Sulfur dioxide (SO(2)) was significantly associated only with white cell counts, nitrogen dioxide (NO(2)) with platelet counts and fibrinogen, and ozone with none of the outcomes. In two-pollutant models, PM(10) remained a significant predictor of white cell counts controlling for SO(2) but not vice versa. PM(10) was marginally significant in a model for platelet counts with NO(2), and the sign of the NO(2) coefficient was reversed. These results were stable with control for indoor exposures (wood stoves, environmental tobacco smoke, gas stoves, fireplaces), dietary risk factors (saturated fat, alcohol, caffeine intake, n-3 fatty acids), and serum cholesterol. The magnitude of the effects are modest [e.g., 13 microg/dL fibrinogen for an interquartile range (IQR) change in PM(subscript)10(/subscript), 95% confidence interval (CI) 4.6-22.1 mg/dL]. However, the odds ratio of being in the top 10% of fibrinogen for the same IQR change was 1.77 (95% CI 1.26-2.49). These effects provide considerable biologic plausibility to the mortality studies. PM(10), but not gaseous air pollutants, is associated with blood markers of cardiovascular risk, and this may explain epidemiologic associations with early deaths.