Histoplasma capsulatum var. capsulatum, Blastomyces dermatitidis, Coccidioides immitis, Paracoccidioides brasiliensis, and Penicillium marneffei are endemic dimorphic fungi that may infect the respiratory tract. Sporothrix schenkeii, which manifests the typical thermal dimorphism of the endemic dimorphic organisms, does not seem to follow a geographically defined endemic pattern of distribution. Most infections with any of these fungi are initiated by inhalation of conidia in nature. The pulmonary infection may be asymptomatic and resolve spontaneously, but reactivation may occur subsequently. Any of these fungi may disseminate from the lungs to other organs. These fungi routinely infect persons with apparently normal immunity and hence are named primary fungal pathogens. The fungi usually are contained by alveolar macrophages which are modulated by T lymphocytes, producing granulomatous inflammatory response for H. capsulatum, P. brasiliensis, and P. marneffei. A combined acute or pyogenic and chronic inflammatory response is often observed with C. immitis and B. dermatitidis. More than 95% of cases of histoplasmosis, coccidioidomycosis, and paracoccidioidomycosis are estimated to be self-limiting. In most cases the only evidence of infection is the development of an immune response, which is manifested by the production of specific antibodies, development of precipitins and complement-fixing antibodies. The small percentage of these events that advance to progressive pulmonary infection or clinically overt disseminated infection are often associated with predisposing risk factors, particularly underlying defects in HIV-infected hosts or patients receiving corticosteroids. The dimorphic fungi that cause systemic mycoses are identified by direct microscopic examination of specimens, by isolation and characterization of the fungus in cultures, by DNA probing of isolates, or by demonstration of specific exoantigens produced in culture.