Although Histoplasma capsulatum is not generally considered an opportunistic organism, we have seen five corticosteroid-treated patients in whom disseminated histoplasmosis (DH) developed. Persistent, unexplained fever was the predominant symptom in each. Death was directly attributable to DH in four. The interval from onset of symptoms to diagnosis ranged from 11 to 75 days; delay in diagnosis adversely affected prognosis. Culture of the bone marrow appears to be the best diagnostic study. The pathologic features of DH in immunocompromised hosts are the presence of large numbers of Histoplasma yeast forms within macrophages, absence of discrete granulomas, and a reduced or absent inflammatory response. Histoplasma capsulatum should be considered as a possible cause in any immunosuppressed patient with unexplained fever, especially if the patient has been receiving corticosteroid therapy. © 1978 American Medical Association. All rights reserved.