We evaluated the effect of air pollution exposure during pregnancy on the occurrence of preterm birth in a cohort of 97,518 neonates born in Southern California. We used measurements of carbon monoxide (CO), nitrogen dioxide, ozone, and particulate matter less than 10 μm (PM10) collected at 17 air-quality-monitoring stations to create average exposure estimates for periods of pregnancy. We calculated crude and adjusted risk ratios (RRs) for premature birth by period-specific ambient pollution levels. We observed a 20% increase in preterm birth per 50-μg increase in ambient PM10 levels averaged over 6 weeks before birth [RRcrude = 1.20; 95% confidence interval (CI) = 1.09–1.33] and a 16% increase when averaging over the first month of pregnancy (RRcrude = 1.16; 95% CI = 1.06–1.26). PM10 effects showed no regional pattern. CO exposure 6 weeks before birth consistently exhibited an effect only for the inland regions (RRcrude= 1.13; 95% CI = 1.08–1.18 per 3 parts per million), and during the first month of pregnancy, the effect was weak for all stations (RRcrude = 1.04; 95% CI = 1.01–1.09 per 3 parts per million). Exposure to increased levels of ambient PM10 and possibly CO during pregnancy may contribute to the occurrence of preterm births in Southern California.