Sixty-one patients were treated with combination chemotherapy (T-7) for biopsy-proved, fully malignant, osteogenic sarcoma (OS) of the extremity. Chemotherapy consisted of the combination of bleomycin, cyclophosphamide, and dactinomycin, followed in 2 weeks by vincristine and high-dose methotrexate (HDMTX) given in doses of 8 g/m2 for adolescents and 12 g/m2 for children 12 years old or younger with citrovorum factor rescue. The HDMTX was administered weekly for 4 weeks. One week following the 4 HDMTX treatments, adriamycin (ADR) was given at a dose of 90 mg/m2 for 2 days. Two weeks after the ADR, 2 additional doses of HDMTX were given before surgery. Thirty-eight of the 61 patients were referred before amputation and underwent preoperative chemotherapy for approximately 3 months. After surgery, chemotherapy was resumed. Of the 61 consecutive patients with primary OS entered in the T-7 protocol, 54 (88%) remained free of disease for more than 8 to over 35 months (median 18+ mo), with a projected 3-year disease-free survival in excess of 80%. Of the 38 receiving T-7 chemotherapy before surgery, 28 demonstrated a near complete or complete lack of viable tumor cells on examination of the resected primary tumors. All 28 are surviving free of disease. Nine of the 10 patients less than 12 years of age remain free of disease from over 12 to more than 35 months (median 24+ mo). A significant increase in disease-free survival in the younger patients could presumably be attributed to the use of 12 g HDMTX/m2 in that age group. The prognostic value of the effect of preoperative chemotherapy on the primary tumor is statistically highly significant. These data indicated that preoperative chemotherapy with the proper dose of HDMTX would be valuable in all patients with OS.