ISEE-0456 Background and Objective: Numerous epidemiologic studies have shown an association of cardiovascular disease (CVD) with fine particulate air pollution (PM2.5); altered cardiac autonomic balance has been suggested as a possible biological pathway. Metabolic diseases, such as type-2 diabetes, have been suggested to confer susceptibility to particle toxicity on CVD. We examined the associations of PM2.5 with heart rate variability (HRV), a marker of cardiac autonomic function, and whether metabolic syndrome (MetS) modified these associations. Methods: Standard deviation of NN intervals (SDNN) and the root mean square of successive differences in NN intervals (rMSSD) were measured in 5,465 persons aged 45-84 years who were free of cardiovascular disease at the Multi-Ethnic Study of Atherosclerosis baseline exam (2000-2002). Data from U.S. Environmental Protection Agency monitors were used to estimate ambient PM2.5 concentrations (averages up to 60 days prior to the HRV measurement) at participant residences. MetS was defined as having three or more of the following criteria: abdominal obesity, hypertriglyceridemia, low high-density lipoprotein cholesterol, high blood pressure, and high fasting glucose. Results: After controlling for confounders, an interquartile range increase in 2-day average PM2.5 (10.2 μg/m3) was marginally associated with a 1.7% decrease in SDNN (95% confidence interval (CI), −3.5%, 0.2%; P = 0.08) and a 1.8% decrease in rMSSD (95% CI, −3.9%, 0.2%; P = 0.08). Associations were stronger among individuals with MetS than those without MetS: an interquartile range elevation in 2-day PM2.5 was associated with a 5.7% decrease in rMSSD (95% CI, −8.9%, −2.4%) among subjects with MetS, whereas almost no change was found among subjects without MetS (P-interaction = 0.005). Similar effect modification was observed in SDNN. No significant effect modification by individual components of MetS was found. Conclusion: These findings suggest an association of PM2.5 with HRV, particularly among persons with MetS.