A patient who has had three distinct recurrences of disseminated histoplasmosis over 22 years is presented. Measurements of cellular and humoral immune response to histoplasmin antigens were compared with previously reported data. Although initially sulfisoxazole therapy led to regression of disease, over the past 13 years she has required three courses of amphotericin B, each time with resolution of signs and symptoms. Despite minimal evidence of a cellular or humoral immune response to this organism, the patient has done well. Although disseminated histoplasmosis is often a fatal disease, this woman has tolerated the infection well.