The use of adjuvant systemic chemotherapy in the management of patients with localized Ewing's sarcoma is providing indications of modifying the usually relentless clinical course of disease observed for most patients who receive local treatment directed only at the primary site. Evidence for this includes not only increasing disease-free intervals after initial treatment, but also the development of isolated intracranial metastases, presumably the consequence of selective anatomic protection afforded by a physiologic (blood-brain) barrier. The present adjuvant program includes systemic chemotherapy with cytoxan, actinomycin D, and vincristine, in addition to prophylactic treatment of the central nervous system with whole brain irradiation and intrathecal methotrexate. The need to centralize treatment of these relatively uncommon cases is discussed.