The structure-activity relationship of polycyclic aromatic hydrocarbon-induced immunosuppression was investigated using the antibody-forming cell response to sheep erythrocytes. Ten polycyclic aromatic hydrocarbons were evaluated following 14 days of subchronic exposure in female B6C3F1 mice. Additionally, the immunotoxicity of benzo(a)pyrene and 3 of its congeners was evaluated following acute exposure. The immunosuppression observed following both subchronic and acute exposure was similar to the structure-activity relationship observed for the carcinogenicity of the compounds tested. Anthracene, chrysene, benzo(e)pyrene and perylene did not significantly suppress the antibody-forming cell response compared to the corn oil vehicle controls. Benz(a)anthracene, benzo(a)pyrene, dibenz(a,c)anthracene, and dibenz(a,h)anthracene suppressed the antibody-forming cell response by 55 to 91%. The greatest suppression was observed with the 3-methylcholanthrene and 7,12,-dimethylbenz(a)anthracene. Studies using mice with different susceptibility to aryl hydrocarbon hydroxylase induction demonstrated that susceptible mice (B6C3F1) were not as immunosuppressed following exposure to polycyclic aromatic hydrocarbons as were nonsusceptible mice (DBA/2).