Several epidemiological studies have indicated that female tobacco smokers may be at higher risk of lung cancer than males. In a study of lung cancer cases, we have found that female smokers had a significantly higher level of aromatic/hydrophobic DNA adducts in their nontumor lung tissue (15.39+/-9.47 adducts/10(8) nucleotides, n = 29) than male smokers (12.08+/-8.14, a = 93; P = 0.047). Females had significantly higher levels of adducts/pack-year (females 0.95+/-0.82 adducts/pack-year and males 0.46+/-0.46; P = 0.0004) and adducts/cigaret/day (females 1.48+/-1.29 and males 0.89+/-0.74, P = 0.015). By quantitative reverse transcription-PCR, it was found that female smokers exhibited a significantly higher expression level of lung CYP1A1 (494+/-334 CYP1A1 mRNA/10(6) glyceraldehyde-3-phophate dehydrogenase mRNA, n = 15) compared with males (210+/-208, n = 12; P = 0.016). Furthermore, for both sexes combined a significant correlation between CYP1A1 expression and DNA adduct level was found (r = 0.50, P = 0.009). In conclusion, the observed sex difference in aromatic/hydrophobic DNA adduct levels may at least in part be explained by different levels of CYP1A1 expression.