We have analyzed the survival data for 117 patients with Ewing's sarcoma treated at the National Cancer Institute since 1964. Treatment consisted of local irradiation to the primary site and a series of increasingly intensive systemic chemotherapy regimens. Four protocols were used with varying numbers of patients in each treatment group. When survival results were compared by treatment group, an overall difference in favor of the most recent treatment regimens was demonstrated (P less than 0.03). When results were evaluated by treatment group according to the site of primary disease, a significant difference was found only for patients who presented with primary lesions of the central axis and without metastases (P less than 0.001). However, we noted a statistically significant correlation of survival with 1) site of primary disease (P less than 0.001), 2) serum lactate dehydrogenase (LDH) level at presentation (P less than 0.0001), and 3) metastatic status at presentation (P less than 0.0001), irrespective of treatment protocol. When the results were reassessed after adjustment for these factors, no significant difference in survival remained. We concluded that further studies, in which stratification for site of primary disease and LDH levels would be used, are necessary to clarify the role of intensive adjuvant chemotherapy in Ewing's sarcoma.