Conventional treatment for high grade and large sarcomas uses a radical surgical approach, including amputation, in many patients. We evaluated a limb-sparing treatment approach using preoperative regional Adriamycin chemotherapy and rapid-fraction radiation therapy. Thirty patients with soft tissue or skeletal sarcoma were treated in a prospective, nonrandomized clinical trial to evaluate local disease control and limb salvage in these patients who would otherwise require amputation or face a high risk of local recurrence with surgical excision. Almost all patients had large tumors with grade III histologic findings. All patients had a three day intra-arterial regional chemotherapy infusion with Adriamycin (100 milligrams total dose), followed within ten days by rapid-fraction irradiation (3,000 rads over a two week period) prior to surgical excision of the tumor. The size and location of the sarcoma permitted only a marginal resection in one-half of the patients, while the remainder could be excised in a three dimensional en bloc manner. Almost all patients received postoperative systemic Adriamycin chemotherapy (450 milligrams per square meter given intravenously over a six month period). Two of six patients with significant wound complications later required amputation. Only one patient (3 per cent) has had a local recurrence of sarcoma develop after a mean follow-up of 22 months (range nine to 42 months), and 90 per cent of the patients have a useful extremity. The three year survival rate was 68 per cent for soft tissue sarcomas, compared with an expected survival rate of 38 per cent for published historical control studies. The patient with osteogenic sarcoma has a projected 83 per cent survival rate at 18 months after treatment. This multimodality approach is an effective treatment for local disease control in patients with high risk sarcoma. It permits limb salvage in most patients without compromising the survival rates.