Candida albicans infection is common in immunocompromised patients. The role of fixed tissue macrophages (Mphi), including Kupffer cells (KC) and peritoneal macrophages (PMphi), in host defense against C. albicans is unclear. This study examined murine Mphi candidacidal mechanisms and evaluated the in vitro role of the macrophage-activating factor IFN-gamma in augmenting these mechanisms. The effect of in vivo administration of IFN-gamma on survival aftrer lethal C. albicans challenge in the murine system was also assessed. Percent PMphi and KC ingestion of C. albicans were similar. Prior opsonization of Candida increased the percentage of Mphi ingestion of this pathogen. PMphi and KC phagocytic function was similar for both nonopsonized and opsonized C. albicans, but KC demonstrated markedly decreased ability to kill this pathogen (O2-, Candida killing). IFN-gamma enhanced KC and PMphi candidacidal activity. PMphi and KC Ag presentation was increased in early Candida infection, but diminished in established infection, when the majority of animals died. C. albicans failed to elicit significant amounts of either IL-1 or TNF compared with LPS stimulation of PMphi and KC in vitro. IFN-gamma treatment in vivo was associated with significantly improved survival (p < 0.01).Candida albicans infection is common in immunocompromised patients. The role of fixed tissue macrophages (Mphi), including Kupffer cells (KC) and peritoneal macrophages (PMphi), in host defense against C. albicans is unclear. This study examined murine Mphi candidacidal mechanisms and evaluated the in vitro role of the macrophage-activating factor IFN-gamma in augmenting these mechanisms. The effect of in vivo administration of IFN-gamma on survival aftrer lethal C. albicans challenge in the murine system was also assessed. Percent PMphi and KC ingestion of C. albicans were similar. Prior opsonization of Candida increased the percentage of Mphi ingestion of this pathogen. PMphi and KC phagocytic function was similar for both nonopsonized and opsonized C. albicans, but KC demonstrated markedly decreased ability to kill this pathogen (O2-, Candida killing). IFN-gamma enhanced KC and PMphi candidacidal activity. PMphi and KC Ag presentation was increased in early Candida infection, but diminished in established infection, when the majority of animals died. C. albicans failed to elicit significant amounts of either IL-1 or TNF compared with LPS stimulation of PMphi and KC in vitro. IFN-gamma treatment in vivo was associated with significantly improved survival (p < 0.01).