Between February 1982 and December 1987, 39 patients with Ewing's sarcoma of bone have been treated at the University of Florida with a twice-a-day radiotherapy regimen to their primary lesion, 35 with radiation alone and 4 with a combination of radiation and surgery. Although three separate systemic regimens were used (standard risk, 1982-1987 [SR-1]; high-risk, 1982-1984 [HR-2]; and high-risk, 1985-1987 [HR-3]), the radiotherapy regimen remained constant through the years of the study. Those patients whose soft-tissue mass completely regressed after induction chemotherapy received 5040 cGy (as did patients with no soft-tissue mass at diagnosis), those who had 50% or greater resolution of the soft-tissue mass received 5520 cGy, and those who had less than 50% regression of the soft-tissue mass or progressive disease during induction chemotherapy received 6000 cGy. All patients were treated with 120 cGy twice a day and a 6-hr separation between fractions. Thirteen patients also received 800 cGy of total body radiotherapy (TBI) 1 to 3 months after local radiotherapy as part of their systemic treatment. In the 33 patients treated with radiotherapy alone who were eligible for local control analysis, there have been three local failures to date, all within the first 21 months after diagnosis. The 5-year local control rate was 88% for SR-1, 80% for HR-2, and 92% for HR-3. Local control was not related to total dose, but by design, the patients with the largest lesions and the poorest response to chemotherapy had the highest doses. In the 20 patients presenting with extremity primary lesions, there have been no pathologic fractures. In patients evaluated for limb function, the late effects have been minimal. The twice-a-day regimen used appears to produce good local control rates with improved long-term function as compared with once-a-day regimens.