Adult female B6C3F1 mice received distilled water only or water containing 10, 50, or 250 ppm of cadmium chloride (CdCl2) for 90 days. Body weights were measured weekly. On selected days during exposure and on Day 91, Cd tissue concentrations were measured along with changes in primary antibody responses. On Day 91 mice also received a primary challenge with various infectious agents. T- and B-cell mitogenesis, natural killer (NK) cell function, delayed type hypersensitivity (DTH) as well as macrophage bactericidal activity, and phagocytosis were measured. There was no change in body weight gain, organ weights, or in humoral immunity during treatment even though cadmium had accumulated in significant quantities in the tissues. Compared with controls, exposure to cadmium had no statistically significant effect on mortality and mean survival time following primary or secondary challenge with any of the infectious agents. However, there was a dose-related, increased susceptibility to Herpes simplex type 2 virus. T- and B-lymphocyte proliferation was significantly reduced, and macrophage phagocytosis was significantly increased following cadmium exposure. NK cell activity was augmented, but not significantly. Macrophage bactericidal activity and DTH were not significantly altered.