The immunopathogenesis of invasive aspergillosis and the role played by cytokines are not fully understood. The roles of interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha were investigated in BALB/c mice infected intravenously with 5 x 10(5) Aspergillus 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-gamma, anti-IFN-gamma, TNF-alpha, or anti-TNF-alpha. No deaths occurred among the mice treated with IFN-gamma and TNF-alpha, compared with 40%-80% mortality in the other groups. IFN-gamma- and TNF-alpha-treated mice also had fewer organs from which A. fumigatus could be cultured or demonstrated on histologic examination. These observations suggest that IFN-gamma and TNF-alpha have protective roles in invasive aspergillosis.