Malignant histiocytosis is a fulminant neoplasm resistent to single agent chemotherapy and resulting in death within 6 months. Sixteen patients have received chemotherapy for this disorder between 1965-1975 at Stanford. Nine patients responded to chemotherapy. Responders had a median survival of 23 months from onset of symptoms and a significantly longer survival than non-responders (p = 0.03). The most promising responses were in seven patients treated with a combination of cyclophosphamide, adriamycin, vincristine and prednisone. Five of the seven responded, with two of the five later relapsing and dying, two having equivocal evidence of disease while on chemotherapy for 6 and 9 months, and one free of disease for 17 months after completing 8 months of chemotherapy. Three patients had central nervous system (CNS) relapses, two during peripheral remission. One of these had control of CNS disease with brain irradiation and intrathecal methotrexate, but all three eventually died. It is hoped that with combination chemotherapy and prophylactic CNS treatment, long term disease-free survivals will be achieved.