The purpose of this study was to assess the effect of long-term ambient particulate matter (PM) on risk of fatal coronary heart disease (CHD). A cohort of 3,239 nonsmoking, non-Hispanic white adults was followed for 22 years. Monthly concentrations of ambient air pollutants were obtained from monitoring stations [PM < 10 microm in aerodynamic diameter (PM10), ozone, sulfur dioxide, nitrogen dioxide] or airport visibility data [PM < 2.5 microm in aerodynamic diameter (PM2.5)] and interpolated to ZIP code centroids of work and residence locations. All participants had completed a detailed lifestyle questionnaire at baseline (1976), and follow-up information on environmental tobacco smoke and other personal sources of air pollution were available from four subsequent questionnaires from 1977 through 2000. Persons with prevalent CHD, stroke, or diabetes at baseline (1976) were excluded, and analyses were controlled for a number of potential confounders, including lifestyle. In females, the relative risk (RR) for fatal CHD with each 10-microg/m3 increase in PM2.5 was 1.42 [95% confidence interval (CI), 1.06-1.90] in the single-pollutant model and 2.00 (95% CI, 1.51-2.64) in the two-pollutant model with O3. Corresponding RRs for a 10-microg/m3 increase in PM(10-2.5) and PM10 were 1.62 and 1.45, respectively, in all females and 1.85 and 1.52 in postmenopausal females. No associations were found in males. A positive association with fatal CHD was found with all three PM fractions in females but not in males. The risk estimates were strengthened when adjusting for gaseous pollutants, especially O3, and were highest for PM2.5. These findings could have great implications for policy regulations.