Primary treatment of large and massive adult sarcomas with iododeoxyuridine and aggressive hyperfractionated irradiation. For a decade, the authors have experimented with treatment for unresectable adult soft tissue and bony sarcomas. Over the last 6 years, they have combined hyperfractionated radiation therapy and intravenous iododeoxyuridine as a radiosensitizer, in regimens designed to minimize toxicity and permit delivery of aggressive radiation therapy. Patients with solitary lesions and those with metastasis (38%) were treated in the hope of both potential cure in some and durable palliation in others. The most formidable of these cancers have been those that are large or massive, often requiring five or more fields and extensive treatment planning. The authors report results from 36 patients with large unresectable sarcomas (tumors ranging from 5 to 35 cm; average 14 cm) treated with hyperfractionated radiation therapy, with a minimum follow-up of 1 year, follow-up of 4 or more years (in 50%), or follow-up until death. Overall local control has been 60%, with control of 66% of lesions from 5 to 9 cm, 63% of those from 10 to 14 cm, 63% of those from 15 to 19 cm, and 57% of those greater than 20 to 40 cm. Morbidity has been modest. This experience compares favorably with the authors' earlier trials with misonidazole, and toxicity has been reduced considerably. 