Benzo[a]pyrene (BP) is a ubiquitous carcinogen found in tobacco smoke, burning of fossil fuels, and our diet. Formation of BP diol epoxide (BPDE)-DNA adducts due to human exposure is most likely to be at very low levels that are beyond the sensitivity of routine radioimmunoassay and chromatographic analyses. Thus, ultrasensitive enzymatic radioimmunoassay (USERIA), enzyme-linked immunosorbentassay (ELISA), and synchronous scanning fluorimetry have been employed to detect and quantitate BPDE-DNA adducts in human at high cancer risk due in part to BP exposure. DNA isolated from white blood cells of asphalt workers (roofers) and foundry workers and DNA from lung tissue, bronchial washings, and alveolar macrophages of lung cancer patients and smokers are being investigated. Putative BPDE-DNA adducts have been detected in several of the high-risk individuales. Antibodies to BPDE-DNA adducts were also found in sera from those workers. These data suggest that the activation of BP to its ultimate carcinogen as well as formation of adducts with DNA occurs in humans. Preliminary evidence indicates that other polycyclic aromatic hydrocarbons (e.g., chrysene and benzo(a)anthracene, DNA adducts) may also evoke an immune response in humans.