We have evaluated the efficacy of voriconazole (VRC) in a murine model of systemic infection by Scedosporium apiospermum. The survival of mice treated with VRC at 5, 20, or 40 mg/kg/day was greater than that of the control group (P less than or equal to 0.0009). VRC reduced the tissue burden in the spleen and brain (P < 0.001 in both organs) in comparison with that of the control group.