The virulence of Exophiala dermatitidis, E. oligosperma and E. xenobiotica, three of the most common members of the genus that cause human infections, was evaluated using experimental models of disseminated infection in immunocompromised mice. Exophiala dermatitidis, and to a lesser extent E. oligosperma, were the two species causing the highest mortality, while mice infected with E. xenobiotica had the lowest mortality. Tissue burden and histopathology studies demonstrated the neurotropism of E. dermatitidis, while E. oligosperma and E. xenobiotica had a limited capacity for invading brain tissue. These models could be useful for testing new therapies against Exophiala infections.