The effect of recombinant rat interferonγ (rIFN-γ) on acute disseminated Candida albicans infection in mice was investigated. Outgrowth of Candida albicans in kidneys, spleen, and liver of mice treated with one intravenous (iv) dose ofrIFN-γ before iv injection of 5 X lOs cfu of Candida albicans was significantly lower than in controls over 7 days. rIFN-γ was protective when given 1 day before, simultaneously with, or 1-3 days after infection but not when given 3 days before. In mice pretreated with hydrocortisone acetate, rIFN-γ significantly reduced the outgrowth only when 10³ cfu of Candida albicans was injected. Injection of rIFN-γ did not reduce the outgrowth of C. albieans in cyclophosphamide-pretreated mice and significantly increased the capacity of peripheral blood and exudate peritoneal granulocytes to kill Candida albicans in vitro. Thus, rIFN-γ enhances host resistance against acute disseminated Candida albicans infection in mice through activation of polymorphonuclear leukocytes.