The immunopathogenesis of invasive aspergillosis and the role played by cytokines are not fully understood. The roles of interferon (IFN)-γ and tumor necrosis factor (TNF)-α were investigated in BALB/c mice infected intravenously with 5 × 105Aspergillus fumigatus conidia. Eight groups of animals were studied, including 2 control groups (mice only infected with A. fumigatus and those given cortisone acetate and infected with A. fumigatus) and 6 groups of infected mice either treated or not treated with cortisone acetate and given IFN-γ, anti-IFN-γ, TNF-α, or anti-TNF-α. No deaths occurred among the mice treated with IFN-γ and TNF-α, compared with 40%–80% mortality in the other groups. IFN-γ- and TNF-α-treated mice also had fewer organs from which A. fumigatus could be cultured or demonstrated on histologic examination. These observations suggest that IFN-γ and TNF-α have protective roles in invasive aspergillosis.