Epidemiologic studies demonstrate increased cancer incidence among workers exposed to polycyclic aromatic hydrocarbons (PAH) and metals, probably through cumulative oxidative DNA damage in response to carcinogens. Boilermakers are exposed to particulates of residual oil fly ash (ROFA) and metal fume that contain carcinogenic PAH and metals. We conducted a repeated-measures cohort study in boilermakers during the overhaul of an oil-fired boiler to determine a possible association between the level of 8-hydroxy-2'-deoxyguanosine (8-OH-dG; an oxidative injury biomarker) and biomarkers of PAH (1-hydroxypyrene; 1-OHP) and metal exposure. Preshift and postshift urine samples were analyzed for 8-OH-dG, cotinine, 1-OHP, and metals. Generalized estimating equations were used to model the multivariate relationship of 8-OH-dG to the explanatory variables of interest. Biomarker levels were determined for 181 urine samples from 20 male subjects (mean age 45 years, 50% smokers). Metal and 1-OHP levels increased cross-week and were affected by smoking status. Levels of 8-OH-dG were higher in nonsmokers at the start of the workweek yet declined after occupational exposure to similar levels as in smokers. Multivariate analysis indicated that metal x cotinine interaction terms for nickel, vanadium, chromium, and copper were significantly associated with the 8-OH-dG level, but there were differential effects depending on the metal. This study suggests that oxidative DNA damage in boilermakers is influenced by the interaction between occupational exposures and smoking status. In addition, boilermakers may have reduced ability to repair damaged DNA after ROFA and metal fume exposure. This finding has clinical relevance because these exposures may increase the cancer susceptibility of boilermakers.