Endogenous interleukin (IL)-18 is necessary for host defense against candidiasis. Prophylactic treatment of Candida albicans-infected mice with recombinant murine (r) IL-18 decreased mortality, which was accompanied by a decreased outgrowth of yeasts in the kidneys 1 day after infection. Therapeutic administration of rIL-18 also resulted in decreased outgrowth of C. albicans in the kidneys and increased levels of interferon- gamma, both in the circulation and after in vitro stimulation of splenocytes with C. albicans. Histopathologic analysis of the kidneys showed increased inflammation and decreased growth of C. albicans in rIL-18-treated mice. In conclusion, rIL-18 improves outcome of disseminated candidiasis in mice and may prove useful as adjuvant immunotherapy of fungal infections.