Coccidioides immitis is a fungus endemic to the southwestern United States. Susceptible hosts, including blacks, Hispanics, Filipinos, Native Americans, and those with compromised immunity, may develop disseminated disease, including fungemia. We retrospectively reviewed the records of all patients (n = 33) with Coccidioides immitis fungemia (CIF) at a 550-bed public hospital in Phoenix, Arizona, from 1990 to 2002. This is the largest reported series of CIF. The purpose of the study was to review the incidence, signs, symptoms, and outcomes of CIF. Twenty-nine patients had human immunodeficiency virus infection. CIF was associated with sepsis, end-stage alcoholic liver disease, and diabetes in four patients. Survival was poor; 24 of the 33 patients died within 28 days. CIF manifested as a systemic inflammatory response syndrome with progressive cardiorespiratory failure. Despite fluid loading, infusion of vasoactive agents, and mechanical ventilation with positive end-expiratory pressure, patients typically experienced a rapidly progressive course and death. CIF portends an ominous prognosis and typically occurs in the setting of advanced human immunodeficiency virus or medical or surgical crises.