Forty-nine patients with localized osteosarcoma of the extremities were treated with a new protocol of neoadjuvant chemotherapy. Preoperatively the patients received high-dose methotrexate intravenously, followed after a week by cisplatinum intra-arterially for a continuous infusion over a 72-hour period, plus adriamycin intravenously infused over an 8-hour period. In all cases the clinical and radiographic response was good and in 44 cases (89.7%) it was possible to perform conservative surgery. The histologic examination of the surgical specimen resulted in necrosis being "good" (greater than or equal to 90% of necrosis) in 41 patients (83.6%). This percentage of "good necrosis" was significantly higher than the percentage previously obtained in our Center as well as in others for preoperative treatment of this tumor. Up to now, patients with localized osteosarcoma of the extremities who showed a good histologic response to the preoperative chemotherapy have had a very good prognosis (82% of patients are continuously disease-free). These results suggest that this new regimen represents a substantial improvement in the treatment of this disease.