Coccidioidomycosis in human-immunodeficiency virus-infected patients poses frequent and significant problems. Most cases are presently concentrated in regions highly endemic for the fungus. Infection most frequently involves the lungs, and diffuse reticulonodular infiltrates are typical. Disease has also been evident in extrapulmonary sites including meningitis. When progressive disease occurs, most patients already have low CD4 lymphocyte counts. In such cases, effective therapies have included amphotericin B, ketoconazole, and newer investigational agents such as itraconazole, and fluconazole. Although coccidioidal infections have developed in only a few patients away from the endemic regions, those that have suggest that reactivation is possible.