The effect of recombinant rat interferon-gamma (rIFN-gamma) on acute disseminated Candida albicans infection in mice was investigated. Outgrowth of C. albicans in kidneys, spleen, and liver of mice treated with one intravenous (iv) dose of rIFN-gamma before iv injection of 5 x 10(5) cfu of C. albicans was significantly lower than in controls over 7 days. rIFN-gamma 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-gamma significantly reduced the outgrowth only when 10(3) cfu of C. albicans was injected. Injection of rIFN-gamma did not reduce the outgrowth of C. albicans in cyclophosphamide-pretreated mice and significantly increased the capacity of peripheral blood and exudate peritoneal granulocytes to kill C. albicans in vitro. Thus, rIFN-gamma enhances host resistance against acute disseminated C. albicans infection in mice through activation of polymorphonuclear leukocytes.