The histopathology of clinical isolates of Scedosporium apiospermum, Scedosporium boydii, and Scedosporium aurantiacum in immunosuppressed mice was evaluated. The organs most affected were the brain, kidneys, and spleen. S. aurantiacum produced more tissue damage than the other two species. Amphotericin B (AMB) was ineffective in the treatment of murine infections caused by such isolates, and posaconazole and voriconazole showed efficacy that correlated with the in vitro susceptibility data.