The purpose of this study was to determine the efficacy of salvage chemotherapy with, P-IMVP-16/CBDCA, consisting of carboplatin (CBDCA), etoposide (VP-16), ifosfamide (IFM), and methotrexate (MTX), for patients with aggressive non-Hodgkin's lymphoma (NHL) who had previously received CHOP [a regimen of cyclophosphamide, hydroxydaunomycin, Oncovin (vincristine), and prednisolone], as first-line chemotherapy. The 45 consecutively enrolled patients received methylprednisolone (mPSL) 1000 mg per body for 3 d (from day 1 to day 3), IFM 1000 mg/m(2) for 5 d (from day 1 to day 5), MTX 30 mg/m(2) on day 3 and day 10, VP-16 80 mg/m(2) for 3 d (from day 1 to day 3), and CBDCA 300 mg/m(2) on day 1, with granulocyte colony-stimulating factor every 21 d. Patients 70 yr of age or older were given 75% of the standard dose. The response rate [complete response (CR) plus partial response (PR)] was 55.6% (25/45), including 12 (26.7%) CR and 13 (28.9%) PR. The overall survival rate for the 45 patients was 31.1% at 1 yr and 17.3% at 2 yr. The failure-free survival rate for the 45 patients was 6.7% at 1 yr and 4.4% at 2 yr. The survival rate for the 25 responders was 48.0% at 1 yr and 24.0% at 2 yr, and the survival rate for the 20 non-responders was 10.0% at 1 yr (P<0.001). Multivariate analysis demonstrated that prior chemotherapy (reduced-dose CHOP for age 70 yr or older) and the number of cases of extranodal involvement (>1) were significant unfavorable factors for overall survival. Although the major toxicity was neutropenia, no patient died of infection related to neutropenia. Non-hematological adverse effects were predominantly mild and tolerable. Unfortunately, the clinical outcome with P-IMVP-16/CBDCA was unfavorable, possibly because the study comprised consecutive patients who had received identified intensive chemotherapy, such as biweekly CHOP. Salvage chemotherapy with P-IMVP-16/CBDCA is not sufficient to cure relapsed or refractory aggressive NHL. Aggressive NHL should be cured by first-line chemotherapy with or without hematopoietic stem cell transplantation.