Following a fatal case of Cryptococcus neoformans meningitis in a child with X-linked hyper-immunoglobulin M syndrome (XHIGM), we evaluated the fungal isolate in an experimental infection in a mouse model with respect to microbiology, epidemiology, virulence and response to therapy. The minimum inhibitory concentrations for antifungals in the susceptibility test were 0.5mg/L for amphotericin B, 4.0mg/L for fluconazole and 0.12mg/L for voriconazole. Evaluation of pathogenicity by means of an experimental infection in BALB/c mice showed that fungus isolated from the blood and cerebrospinal fluid of the child was able to disseminate, reaching the spleen, lungs and brain, where it caused significant macroscopic alterations in the size and texture of each organ. Treatment of infected mice with amphotericin B reduced the fungal load in the spleen and lungs, but not in the brain.