Peripheral blood DNA adducts have been considered an acceptable surrogate for target tissues and possibly predictive of cancer risk. A group of 114 workers exposed to traffic pollution and a random sample of 100 residents were drawn from the EPIC cohort in Florence, a population recently shown to present increased DNA adduct levels (Palli et al., Int J Cancer 2000;87:444–51). DNA bulky adducts and 3 DNA repair gene polymorphisms were analyzed in peripheral leukocytes donated at enrollment, by using 32P-postlabeling and PCR methods, respectively. Adduct levels were significantly higher for traffic workers among never smokers (p = 0.03) and light current smokers (p = 0.003). In both groups, urban residents tended to show higher levels than those living in suburban areas, and a seasonal trend emerged with adduct levels being highest in summer and lowest in winter. Traffic workers with at least 1 variant allele for XPD-Lys751Gln polymorphism had significantly higher levels in comparison to workers with 2 common alleles (p = 0.02). A multivariate analysis (after adjustment for age, season, area of residence, smoking, XPD-Lys751Gln genotype and antioxidant intake) showed a significant 2-fold association between occupational exposure and higher levels of adducts (odds ratio 2.1; 95% confidence interval 1.1–4.2), in agreement with recent pooled estimates of increased lung cancer risk for similar job titles. Our results suggest that traffic workers and the general population in Florence are exposed to high levels of genotoxic agents related to vehicle emissions. Photochemical pollution in warmer months might be responsible for the seasonal trend of genotoxic damage in this Mediterranean urbanized area. © 2001 Wiley-Liss, Inc.