Eight immunologically suppressed (immunosuppressed) patients with disseminated histoplasmosis were seen in 36 months in a nonendemic area in which greater than 90 per cent of young adults have a negative histoplasmin skin test. Evidence suggesting endogenous reinfection as a possible mechanism for these patients include (1) virtual absence of cases in nonimmunosuppressed patients; (2) absence of cases of disseminated histoplasmosis in children during the time period of the study; (3) known previous residence in endemic areas by five of eight patients; (4) absence of an acute respiratory illness preceding dissemination; and (5) onset of disseminated disease shortly after initiation of high dose glucocorticoid therapy in very sick patients with little, if any, chance of environmental exposure. Histoplasmosis should be considered as a possible opportunist in undiagnosed febrile illnesses in compromised hosts. This is true even in nonendemic areas, especially when history of previous residence in an endemic area can be obtained. Suspicion should be greatest when high dose glucocorticoid therapy has recently been started. The clinical picture of disseminated histoplasmosis in these patients is not specific. Rapid diagnosis is often possible on bone marrow or liver biopsy once the diagnosis is considered. Cultures of these tissues usually yield the organism even when the histopathologic examination is negative. Early diagnosis is especially important because specific therapy is available. Rapid initiation of therapy can be life-saving as shown by four of our eight patients.