The effect of recombinant interferon-gamma (rIFN-gamma) on Cryptococcus neoformans infection was investigated in vivo. BALB/c mice were injected intravenously with 2 x 10(6) C. neoformans. rIFN-gamma alone (10 micrograms intraperitoneally 18 h before, at, 24 h after infection) significantly increased the survival and decreased the colony-forming unit counts in the lungs compared with untreated mice. rIFN-gamma association significantly enhanced the effect of a single dose of amphotericin B (0.25 mg/kg 24 h after infection) to prolong mouse survival and to reduce colony counts in the brain. Tumor necrosis factor-alpha levels, measured in spleen 3, 6, and 24 h after infection, were not increased by rIFN-gamma. These results suggest that exogenous rIFN-gamma might improve the effect of antifungal therapy during cryptococcosis.