Immunohistochemical techniques using monoclonal antibodies to T lymphocyte subpopulations were used to characterize further the granulomas of disseminated coccidioidomycosis. Skin biopsy specimens from patients with disseminated coccidioidomycosis were studied and compared with tissues from experimentally infected mice. In human skin biopsy specimens and infected mouse tissues, discrete granulomata were seen in which T lymphocytes formed a peripheral mantle surrounding central aggregates of macrophages. This unusual pattern of granuloma formation may represent an ineffective host response because these individuals are unable to clear their infection. Because of the close similarity of immunopathology in both human and mouse infections, the mouse model should serve as a useful tool in elucidating the factors contributing to ineffective host responses in systemic fungal infections.