Polyaromatic hydrocarbons (PAHs) are chemicals that are widely employed to examine the complex mechanisms by which chemicals cause cancer. While it is clear that the tumors that carcinogenic PAHs produce elicit an immune response, the interplay between host immune defense mechanisms and earlier stages in the cutaneous carcinogenesis pathway has received little attention. Studies from our laboratories have shown that topical application of several different PAHs to mice results in the development of an antigen-specific cell-mediated immune response to them. The response is genetically determined and is mediated by CD8+ T cells. Development of a cell-mediated immune response is associated with resistance to dimethylbenz(a)anthracene tumorigenesis. These findings are consistent with the hypothesis that host defense mechanisms against PAHs help to protect individuals from the carcinogenic actions of these agents. This may form the basis for novel immunopreventive strategies for individuals at high risk for development of tumors produced by PAHs. Copyright © 2001 S. Karger AG, Basel.