Mercury can induce systemic autoimmunity in susceptible mouse strains characterized by a T-cell-dependent polyclonal B-cell activation, increased serum levels of IgG1 and IgE antibodies, production of autoantibodies, and the formation of immune complexes in the kidneys. However, certain resistant mouse strains do not show any of the autoimmune manifestations after mercury injection. Th1/Th2 dichotomy has been proposed to be responsible for resistance and susceptibility, respectively. Immunosuppression has also been suggested in resistant animals after mercury injection. To test whether immunosuppression or a biased Th1-type response was induced by mercury in resistant DBA/2 mice, we injected DBA/2 mice with mercury for 1 or 3 weeks and then immunized the mice with horse red blood cells (HRBCs) to study whether the subsequent humoral response to HRBCs was inhibited or skewed to the production of antibodies of IgG2a isotype switched by Th1-type cytokines. We found that there was no reduction of the number of splenic antibody-producing cells in the subsequent response to HRBCs compared with saline-treated mice. By haemagglutination tests, the titers of HRBC-specific antibodies were the same after HRBCs injection in both mercury- and saline-treated DBA/2 mice. There was no increase in total serum IgG2a antibody. Sera of both mercury- and saline-treated mice immunized with HRBCs showed high titres of specific IgM, IgG1 and IgG2a anti-HRBCs antibodies. Surprisingly, 3-week treatment with mercury induced a reduction in the titres of specific IgG2a anti-HRBCs antibodies in DBA/2 mice after immunization with HRBCs. Our results demonstrated that mercury did not induce a general immunosuppression or a biased Th 1-type immune response in resistant DBA/2 mice. The nonresponsiveness in mice resistant to mercury-induced autoimmunity must be due to some other unknown mechanism(s).