To investigate the association between particulate matter with an aerodynamic diameter of less than 2.5 μm (PM2.5 ) exposure during each trimester of pregnancy and development of lower respiratory tract infections (LRTIs) during the first 3 years of life and whether GSTM1 gene polymorphisms modify these effects. This study included 1,180 mother-child pairs from the Cohort for Childhood Origin of Asthma and allergic diseases. The PM2.5 levels during pregnancy were estimated by residential address using land-use regression models based on a national monitoring system. A diagnosis of LRTIs was based on a parental report of a physician's diagnosis. Real-time polymerase chain reaction was used for GSTM1 genotyping. Higher PM2.5 exposure during the third trimester was associated with LRTIs at 1 year of age (aRR, 1.06; 95% CI, 1.00-1.13). This result did not change after adjusting for PM2.5 exposures during the first and second trimesters (aRR, 1.06; 95% CI, 0.99-1.13). This association was significant after adjusting for PM2.5 exposures during first year of age (aRR, 1.08; 95% CI, 1.02-1.15) and exposures to NO2 and ozone at the third trimester (aRR, 1.07; 95% CI, 1.00-1.16). In addition, PM2.5 exposure during the third trimester increased the risk of LRTIs at 1 year of age in cases with the GSTM1 null genotype (aRR, 1.26; 95% CI, 1.01-1.57; P for interaction .20). Higher PM2.5 exposure during the third trimester of pregnancy may increase the susceptibility to LRTIs at 1 year of age. This effect is modified by GSTM1 gene polymorphisms.