Twenty-five children with generalized histiocytosis X were treated with a combination of cyclophosphamide, vinblastine, and prednisone: 8 patients experienced complete response, 8 partial response, 2 imporvement, and 7 no response. Response rates for children over 1 year of age were higher than those reported for single agents. Twelve children are now off therapy with no evidence of disease for 10--50 months. Very poor response rates and high toxicity were seen in children less than 1 year of age. The two infants who eventually achieved CR did so by other therapies. Further trials in combination chemotherapy must weight possible long-term effects of such therapy against the prospect of more rapid disease control.