PURPOSE: We sought to investigate the effect of secondhand smoke exposure on inflammatory markers related to cardiovascular disease. METHODS: During 2001 to 2002, we randomly selected a stratified (age-sex) sample of adults without clinical evidence of cardiovascular disease. Exposure to secondhand smoke (>30 minutes per day and > or =1 day per week) was recorded. Multivariate regression analysis was used to evaluate the effects of exposure to secondhand smoke on levels of C-reactive protein, fibrinogen, homocysteine, and oxidized low-density lipoprotein (LDL) cholesterol, and on white blood cell count. RESULTS: One hundred and thirty-seven (38%) of the 357 men who had never smoked and 211 (33%) of the 638 never-smoking women reported current exposure to secondhand smoke. Compared with those who were not exposed to secondhand smoke, those exposed more than 3 days per week had higher white blood cell counts (by 600 cells per microL; P = 0.02), as well as higher levels of C-reactive protein (by 0.08 mg/dL; P = 0.03), homocysteine (by 0.4 micromol/L; P = 0.002), fibrinogen (by 5.2 mg/dL; P = 0.4), and oxidized LDL cholesterol (by 3.3 mg/dL; P = 0.03), after adjusting for several potential confounders. CONCLUSION: Our findings suggest another pathophysiological mechanism by which exposure to secondhand smoke is associated with the development of atherosclerosis.