To test whether or not diets enriched in w-6 polyunsaturated fatty acids are significantly immunosuppressive, B10.D2, DBA/2, and C3B6F1 mice were fed diets enriched for fatty acids: linoleic (POLY), oleic (MONO), palmitic (SAT), or eicosapentanoic (FISH). The B10.D2 and DBA/2 mice were given injected methylcholanthrene several weeks later, and immune studies were performed several months after carcinogen treatment. In conventional quarters, DBA/2 fed the POLY diet survived poorly, and many were infected with Mycoplasma pulmonis, even if given the vehicle, tractinoin, only. B10.D2 mice survived well unless on the POLY diet and given methylcholanthrene. Nevertheless, only mice on the POLY diet were significantly immunosuppressed, and only T-cell-mediated cutaneous sensitivity reactions were affected. Antibody, natural killer cell, and natural cytotoxic cell responses were not influenced by the diets. The C3B6F1 mice were assessed for immune functions prior to carcinogen (ethylnitrosourea) instillation into the trachea, and no immunosuppression was detected. After instillation, mice on the POLY and MONO diets were suppressed for T-cell cutaneous responses. Deliberate infection with Mycoplasma pulmonis resulted in suppressed cutaneous T-cell responses in the POLY group of C3B6F1 mice, and aspirin partially reversed the immunosuppression. Mice on the FISH diet were resistant to immunosuppression. It is tentatively concluded that diets rich in w-6 polyunsaturated diets, while not directly immunosuppressive, do predispose animals to suppression of certain T-cell-mediated immune responses. This immunosuppression can be "triggered" by infection and/or by exposure to carcinogens.