ISEE-23 Introduction: The biological mechanisms that underlie the reported air pollution-related excess risk of cardiovascular morbidity/mortality are unknown; hypotheses include oxidative stress, altered hemostasis and/or changes in autonomic function. The National Heart, Lung, Blood Institute’s Cardiovascular Health Study (CHS) is a population-based longitudinal study of coronary heart disease and stroke among older women and men. We initiated a CHS Ancillary Study in 1999 to evaluate the subclinical and clinical effects of air pollution. Objective: Evaluate relationship between short-term exposures to O3, NO2, CO, SO2, PM10, PM2.5, PM10–2.5 and clotting factor VII (FVII) and VIII (FVIII) levels. Methods: Continuous enrollment of the main cohort between June 1989 and May 1990, and temporal variation in day-to-day pollutant levels allows evaluation of short-term exposure effects. Baseline data were obtained from the CHS for participants in Allegheny County, PA (n=1275), Forsyth County, NC (n=1305), and Sacramento County, CA (n=1318). Air quality and meteorological data were obtained from the U.S. EPA, CA Air Resources Board or U.S. National Climatic Data Center. Various strategies were used to estimate exposures on days with missing data. Gender-specific single-pollutant linear regression models were used to evaluate effects of 24-hour average pollutant concentrations averaged over exposure periods (EAP) of 2- days (day of exam and previous day (L01)) or 7-days (day of exam and previous 6 days). Natural log transformations of FVII and FVIII were required to meet model assumptions. Final models were adjusted for age-at-exam, Community, 24-hour average temperature (L01), and (in FVII model only) 24-hour average dew point (L01). Results: Across the range of pollutant exposures experienced by the cohort over the 1-year baseline period, small significant effects on population mean levels of FVIII, but not FVII, were observed. A 10-μg/m3 higher level of PM10 (7-day EAP) was associated with higher FVIII levels among women (1.3% (95% CI: 0.12%, 2.6%)) and men (1.5% (95% CI: 0.14%, 2.8%)). PM2.5 was also positively associated with FVIII (women: 2.1% (95% CI: 0.6%, 3.7%); men 2.1% (95% CI: 0.5%, 3.8%)). Perhaps reflecting different mechanism(s)/kinetics of response, among women, mean FVIII levels were inversely related to the 2-day EAP for O3 (−2.3% (95% CI: −4.3%, −0.23%) and PM10–2.5(−2.3% (95% CI: −4.6%, 0.01%). PM10–2.5 (2d-EAP) was also inversely related to FVIII among men (−2.1% (95% CI: −4.9%, 0.73%). These results will be discussed in the context of specific mechanistic hypotheses.