CONTEXT: Exposure to single pollutants e.g. particulate matter (PM) is associated with adverse health effects, but it does not represent a real world scenario that usually involves multiple pollutants. OBJECTIVES: Determine if simultaneous exposure to PM and NO(2) results in synergistic interactions. MATERIALS AND METHODS: Healthy young volunteers were exposed to clean air, nitrogen dioxide (NO(2), 0.5 ppm), concentrated fine particles from Chapel Hill air (PM(2.5)CAPs, 89.5 +/- 10.7 microg/m(3)), or NO(2)+PM(2.5)CAPs for 2 h. Each subject performed intermittent exercise during the exposure. Parameters of heart rate variability (HRV), changes in repolarization, peripheral blood endpoints and lung function were measured before and 1 and 18 h after exposure. Bronchoalveolar lavage (BAL) was performed 18 h after exposure. RESULTS: NO(2) exposure alone increased cholesterol and HDL 18 h after exposure, decreased high frequency component of HRV one and 18 h after exposure, decreased QT variability index 1 h after exposure, and increased LDH in BAL fluid. The only significant change with PM(2.5)CAPs was an increase in HDL 1 h after exposure, likely due to the low concentrations of PM(2.5)CAPs in the exposure chamber. Exposure to both NO(2) and PM(2.5)CAPs increased BAL alpha1-antitrypsin, mean t wave amplitude, the low frequency components of HRV and the LF/HF ratio. These changes were not observed following exposure to NO(2) or PM(2.5)CAPs alone, suggesting possible interactions between the two pollutants. DISCUSSION AND CONCLUSIONS: NO(2) exposure may produce and enhance acute cardiovascular effects of PM(2.5)CAPs. Assessment of health effects by ambient PM should consider its interactions with gaseous copollutants.