Altered IL-6 production regulation is associated with the pathogenesis of chronic inflammatory diseases, lymphoid malignancies, chronic infectious processes and certain types of autoimmune conditions. Here, we examine the effects of pollutants on IL-6 levels in mice serum and in culture supernatants of spleen cells. Mice were treated with vehicles (PBS or olive oil), benzo[alpha]pyrene (B[alpha]P, 100 mg/kg body weight), 2-bromopropane (2-BP, 3.5 g/kg), phenol (21.2 mg/kg), or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, 15 mg/kg). Serum IL-6 levels were significantly increased in the TCDD-treated group at 24 hours and 48 hours after a single exposure, whereas exposure to phenol, B[alpha]P or 2-BP did not cause a significant difference. IL-6 levels in culture supernatants of splenocytes were not affected at 24 hours and 48 hours after a single pollutant treatment. A repeated dose of TCDD (once/week for 4 weeks) resulted in a significant elevation of IL-6 levels in serum and its spontaneous production in culture supernatants of splenocytes. Repeatedly TCDD-treated mice contained more CD11b (Mac-1)-positive cells in the spleen and higher titers of tissue-specific autoantibodies than the vehicle-treated group. These results suggest that repeated exposure to TCDD might impair the regulation of immune response by deregulating the production of IL-6.