We describe the case of a 70-year old female who had developed acute renal failure following high dose methotrexate therapy for malignant lymphoma. Previously, she showed normal renal function and tolerance to high dose methotrexate therapy. Serum methotrexate level reached 9.25 micro mol/L and sustained elevated level for 1 week, although folic acid rescue was intensified to 150 mg intravenously every 3 hours. Therefore, 3 times total plasma exchange and one hemodialysis were performed, and serum methotrexate level returned to normal range. Acute renal failure induced by methotrexate can be complicated by prolonged high serum level of methotrexate, resulting in bone marrow suppression and severe mucositis. To lower the serum methotrexate level, dialysis, plasma exchange, hemoperfusion with charcoal only or combined with hemodialysis and carboxypeptidase-G2 were tried. Successful rescue was obtained by plasma exchange and hemodialysis. No rebound phenomenon was developed.