In recent years, more effective and less toxic treatment protocols have been developed to increase the cure rates in intermediate and high grade non-Hodgkin's lymphoma (NHL). This study was undertaken to investigate the efficacy and toxicity of MWE (ifosfamide, mesna, mitoxantrone and etoposide) combination chemotherapy in patients with intermediate and high grade NHL. Twenty-one patients (16 male, 5 female; age between 26 and 70 years) with NHL were included in the study. An overall response rate of 73% and complete response rate of 56% were achieved and survival rate for responding patients was 80% at the 48th month. Side effects including mild myelosuppression, nausea/vomiting and alopecia were observed. MINE combination seems to be effective and well tolerated without significant toxicity as a first-line therapy in patients with intermediate or high grade NHL.