Fourteen patients with relapsed or refractory acute leukemia received combination chemotherapy of mitoxantrone 6 mg/m2/day intravenously for three to six days and cytosine arabinoside 60 mg/m2/day intravenously over 24 hours continuously for five to ten days. Complete remission was attained in six patients (42.9%) and partial response in two patients (14.3%). Six patients (42.9%) had resistant disease, and four patients (28.6%) died during the myelosuppressive phase. Of the patients achieving complete remission, four relapsed and other two continued complete remission up to 27.3 months. Median remission duration was approximately 10.6 months. No significant difference was found with regard to the efficacy of our regimen between AML and ALL. Hematological toxicity was no more severe than the prior cumulative chemotherapy. Major non-hematologic side effects were nausea and vomiting (71.4%), stomatitis (64.3%) and liver dysfunction (57.1%), which were moderate and manageable, while no cardiotoxicity was observed in any patient. In conclusion, the combination chemotherapy of mitoxantrone and conventional dose cytosine arabinoside is an effective salvage therapy in relapsed or refractory acute leukemia, and our regimen has possible utility as first-line chemotherapy in de novo acute leukemia also.