From December 1989 to July l990, we have tried 70 courses of high-dose methotrexate therapy, which was combined with adriamycin and cisplatin, in the treatment of 13 patients with primary wteogenic sarcoma. The dosage of methotrexate in our protocol was 8 grams per square meter of body surface and the intravenous infusion was done for 4 hours. Using fluorescence polarization immunoassay (FPI) method, we measured the plasma level of methotrexate at 4, 5, 6, B, 24, 48 and 72 hours from the start of infusian. The toxicities were analyzed according to the WHO guidelines. The mean plasma level was 1343.89uM/L at 4 hours (S.D.: 474.63, range: 795.40 to 2870.00), 736.58 (S.D.:291.33, range: l53.00 to 1495.90) at 5 hours, 601.26 (S.D.:329.69, range:36.10 to 1251.20) at 6 hours, 353.44 (S.D.: 179.02, range: 3.60 to 720.23) at 8 hours, 7.32 (S.D.: 9.79, range: 0.08 to 68.50) at 24 hours, 0.40(S.D.: 0.55, range: 0.02 to 3.90) at 48 hours and 0.15 (S.D.: 0.09, range: 0.01 to 0.63) at 72 hours. Twenty two point nine percents at 24 hours and 17.1 percents at 48 hours needed increase of citrovorum factor rescue and 14.3 percents needed prolonged administration of citrovorum factor at 72 hours. Myelosuppression, alteration of hepatic function such as increase of sGOT and sGPT, and other infrequent toxicities were observed, but they were reversible and did not result in permanent dysfunction.