DNA methylation is a potential pathway linking air pollution to disease. Studies indicate that psychological functioning modifies the association between pollution and morbidity. The authors estimated the association of DNA methylation with ambient particulate matter less than 2.5 µm in diameter (PM(2.5)) and black carbon, using mixed models. DNA methylation of the inducible nitric oxide synthase gene, iNOS, and the glucocorticoid receptor gene, GCR, was measured by quantitative polymerase chain reaction pyrosequencing of 1,377 blood samples from 699 elderly male participants in the VA Normative Aging Study (1999-2009). The authors also investigated whether this association was modified by psychological factors including optimism or pessimism, anxiety, and depression. iNOS methylation was decreased after acute exposure to both black carbon and PM(2.5). A 1-μg/m(3) increase in exposure to black carbon in the 4 hours preceding the clinical examination was associated with a 0.9% decrease in 5-methylcytosine (95% CI: 0.4, 1.4) in iNOS, and a 10-μg/m(3) increase in exposure to PM(2.5) was associated with a 0.6% decrease in 5-methylcytosine (95% CI: 0.03, 1.1) in iNOS. Participants with low optimism and high anxiety had associations that were 3-4 times larger than those with high optimism or low anxiety. GCR methylation was not associated with particulate air pollution exposure.