AbstractAdult malignant histiocytosis, also known as histiocytic medullary reticulosis, has been, in the past, considered a very aggressive disorder usually resistant to chemotherapy. Management in the past has included either single agent therapy or splenectomy. Recently, several cases have been reported that have responded favorably to combination chemotherapy. This paper reports on our experience with combination chemotherapy for this disorder. Of three patients treated, all three responded with a complete remission and two remain alive and free of disease at the present time. The outlook for patients with this diagnosis appears to be changing favorably with the advent of new treatment regimens.