The VM*P combination chemotherapy was administered to 13 patients with advanced (Stage III and IV) non-Hodgkin's lymphoma refractory to previous multiagent chemotherapy including cyclophosphamide (EX) and/or adriamycin (ADM). 1) Complete response was obtained in two patients with diffuse histiocytic lymphoma and one patient with diffuse undifferentiated (Burkitt type) lymphoma, and a response rate was 46.2%. 2) Tumor regression in responders was recognized within one week after administration of VM*P, but the duration of response was only 7(2-17) weeks in median (range). 3) Positive correlation was not seen between responsibility and dose of vincristine or methotrexate (MTX), but complete responders were obtained with only over 30 mg/dose of MTX. 4) In spite of resistant cases against EX and/or ADM, complete responders were obtained with VM*P therapy. Clinically, it was shown that cross resistance was minimal among MTX, EX and ADM. 5) Major side effects of VM*P therapy were myelosuppression (75%), hepatotoxicity (46%), and severe infection (23%). Neurotoxicity and nephrotoxicity were rare.