Histoplasmosis and blastomycosis are caused by dimorphic fungi, can be epidemic or endemic, and can produce a spectrum of illness, from subclinical infection to progressive disseminated disease. Diagnosis of both is best made by visualization of yeast in tissue or by culture. Itraconazole is the drug of choice for treatment of both histoplasmosis and blastomycosis, except in cases of life-threatening infection, for which amphotericin B is indicated. A heavy inoculum of Histoplasma capsulatum may cause acute pulmonary infection in an otherwise healthy host, resulting in fever, hypoxia, and pulmonary infiltrates. Opportunistic histoplasmosis develops as chronic pulmonary histoplasmosis in those with a structural defect in the lung (emphysema) or as disseminated histoplasmosis in patients with cellular immune deficiency (due to immunosuppressants or AIDS). Blastomyces dermatitidis causes both pulmonary and extrapulmonary disease. Lung involvement may mimic bacterial pneumonia, while chronic presentations mimic lung cancer or tuberculosis. Skin is the most common extrapulmonary site of disease, followed by bone, prostate, and central nervous system.