Reduced heart rate variability (HRV), a marker of poor cardiac autonomic function, has been associated with air pollution, especially fine particulate matter [< 2.5 μm in aerodynamic diameter (PM 2.5)]. We examined the relationship between HRV [standard deviation of normal-to-normal intervals (SDNN), power in high frequency (HF) and low frequency (LF), and LF:HF ratio] and ambient air pollutants in 497 men from the Normative Aging Study in greater Boston, Massachusetts, seen between November 2000 and October 2003. We examined 4-hr, 24-hr, and 48-hr moving averages of air pollution (PM 2.5, particle number concentration, black carbon, ozone, nitrogen dioxide, sulfur dioxide, carbon monoxide). Controlling for potential confounders, HF decreased 20.8% [95% confidence interval (CI), 4.6–34.2%] and LF:HF ratio increased 18.6% (95% CI, 4.1–35.2%) per SD (8 μg/m 3) increase in 48-hr PM 2.5. LF was reduced by 11.5% (95% CI, 0.4–21.3%) per SD (13 ppb) increment in 4-hr O 3. The associations between HRV and PM 2.5 and O 3 were stronger in people with ischemic heart disease (IHD) and hypertension. The associations observed between SDNN and LF and PM 2.5 were stronger in people with diabetes. People using calcium-channel blockers and beta-blockers had lower associations between O 3 and PM 2.5 with LF. No effect modification by other cardiac medications was found. Exposures to PM 2.5 and O 3 are associated with decreased HRV, and history of IHD, hypertension, and diabetes may confer susceptibility to autonomic dysfunction by air pollution.