The role of macrophages in the resistance of ICR mice to Candida albicans and Salmonella typhimurium was assessed using silica, agent which selectively inactivates macrophages or poly-2-vinylpyridine-N-oxide(PVNO), a lysosomal stabilizing agent. In addition, effect of silica on humoral and cellular immune responses to sheep red blood cells(SRBC) or polyvinylpyroridone(PVP) was examind. Colonyforming units(CFU) of C. albicans or S. typhimurium in the spleen, livers and kidneys of silica-treated or diluent-treated mice were enumerated at various times after infection. Silica was given i. v. to mice at 4 days or 1 day before infection. Although there was no apparent differences in the number of CFU of C. albicans cultured from the spleens or livers of silica-treated and control mice at every assay period, significant differences in the number of CFU of C. albicans in the kidneys of silica-treated and control mice. Namely, silica given to mice 1 day before infection significantly increased the number of CFU of C. albicans in the kidneys at 2, 4 and 6 days after infection, but did not change the number of CFU at 8 days after infection. Silica given to mice at 4 days before infection significantly increased the number CFU in the kidneys at 2 and 4 days after infection, but rather decreased the number of CFU at 8 days after infection. The number of CFU of C. albians cultured from the kidneys of splenectomized which were experimentally infected mice was similar to the number recovered from sham-operated mice at 4 and 8 days postinfection irrespective of time of infection relative to operation. The pretreatment of mice with PVNO appeared to abrogate the silica-induced susceptibility of mice to C. albicans. PVNO alone showed somewhat protective effect against challenge with C. albicans. In contrast, silica treatment did not alter the number of CFU of S. typhimurium recovered from the spleens and kidneys of mice. The administration of silica to mice at 4 days or 1 day before SRBC immunization significantly suppressed delayed-type hypersensitivity(DTH) reactions to SRBC and antibody production to SRBC, a thymus-dependent antigen and PVP, a thymus-independent antigen. These results provide evidence that macrophages play an important role in susceptibility to Candida infection and strongly demonstrated that macrophages play an essential role in the induction of immune responses in mice.