Exposure to environmental tobacco smoke (ETS), which is largely composed of the sidestream cigarette smoke, has been implicated in increased incidence of cancer among nonsmokers. The present study was conducted to compare the potential of mainstream and sidestream cigarette smoke to induce DNA adducts in mice. Groups of female C57Bl and DBA mice were exposed twice daily for 65-70 weeks to mainstream or sidestream smoke from the University of Kentucky reference cigarettes (2R1) in a nose-only exposure system. Animals received a total particulate matter dose of about 16 and 6 mg/kg body weight/exposure and exhibited blood carboxyhemoglobin levels of about 16 and 34%, for mainstream and sidestream smoke-exposed groups, respectively. Pulmonary aryl hydrocarbon hydroxylase (AHH) activity was induced by about 2- to 3-fold in both mainstream and sidestream groups of C57Bl and in mainstream smoke-exposed group of DBA mice, but not in sidestream smoke-exposed DBA mice. An analysis of total DNA adduct levels by the 32P-postlabeling assay showed a significant (12- to 25-fold) increase in the magnitude of preexisting lung DNA adducts in both mainstream and sidestream smoke-exposed C57Bl and DBA mice. Smoke exposures did not affect the total preexisting DNA adducts in liver of either strain. It is concluded that both mainstream and sidestream smoke are capable of enhancing preexisting DNA adducts in the lungs of chronically smoke-exposed mice.