Immunological effects of manganese chloride (MnCl2) were determined in male CD-1 mice injected (ip) daily with MnCl2 (0, 1, 3, or 10 mg/kg) for 4 wk. Liver and spleen weights increased in the 10-mg/kg MnCl2 treatment group. The weights of thymus, kidney, and adrenal glands were not affected by MnCl2 treatment. No significant differences in peripheral erythrocyte or leukocyte counts were observed; however, packed cell volumes decreased in the medium- and high-dose groups. Manganese treatment significantly increased the uptake of [3H]thymidine (3H-TdR) by cultured splenic cells. The lymphoproliferative responses to phytohemagglutinin (PHA) and concanavalin A (Con A) increased at all levels of MnCl2 exposure. No differences in the responses to lipopolysaccharide (LPS) were observed. Mixed lymphocyte responses increased significantly with exposure to 10 mg MnCl2/kg. Another immunological alteration induced by MnCl2 was a dose-dependent immunosuppressive effect on the development of antibody-forming cells. The production of anti-sheep red blood cell antibody (alpha-SRBC) nearly ceased following exposure to 10 mg MnCl2/kg. This effect was apparently reversible, as the number of plaque-forming cells in the 10-mg/kg treatment group increased after MnCl2 treatment had been halted for 2 wk. The alpha-SRBC titer also decreased significantly in the 10-mg/kg treatment group, corresponding to the reduction of antibody producing cells. MnCl2 treatment was immunomodulatory to the reduction of antibody producing cells. MnCl2 treatment was immunomodulatory in male CD-1 mice, as indicated by the increase in mitogen and mixed lymphocyte responses and decrease in antibody production.