An increased risk of some forms of cancer, including lung cancer, among lean individuals has been consistent; however, there is a paucity of biological evidence supporting this relation. Subjects analyzed were 177 healthy Japanese workers who participated in a lifestyle intervention study. The levels of urinary 8-hydroxydeoxyguanosine (8-OHdG), a marker of oxidative DNA damage, were measured using an automated high-pressure liquid chromatography and urinary creatinine levels were adjusted for before statistical analysis. A clear inverse association was found between body mass index (BMI) and 8-OHdG levels among smokers [Pearson correlation coefficient (r) = -0.48], and the association did not materially change after adjustment for potential confounding factors. In contrast, no apparent relation was observed between BMI and 8-OHdG levels among nonsmokers (r = -0.12), although lean nonsmokers had a slightly higher mean of 8-OHdG levels compared with nonlean nonsmokers. The interaction of smoking and BMI reached statistical significance (P = 0.04). Leanness may enhance oxidative DNA damage induced by smoking and thus serve as a marker of host susceptibility to smoking-related cancers.