Sixteen patients with acute refractory or early relapsed leukemias were treated with mitoxantrone (MITOX), etoposide (ETOP) and high dose cytosine arabinoside (HD ARA-C).7 patients with Acute Nonlymphoblastic Leukemia(ANLL) and 3 patients with Acute lymphoblastic Leukemia(ALL) have been treated with a combination of MITOX 12 mg/m2 /m2day IV x 5 days and ETOP 100 mg/m2 /day IV x 5 days. Four patients with ANLL, one patient with ALL and one patients with Chronic Myelogenous Leukemia in Elastic Crisis(CMLBC)received MITOX 10 mg/m2/day IV x 4 days and HD ARA-C 2 g/m212 hours IV x 4 days. In 7 cases of ANLL receiving MITOX + ETOP, 3 achieved complete remission (43%) and 2 achieved partial remission (28%). None of the patients with ALL could achieve remission. In MITOX + HD ARA-C group 2 out of 4 AML patients obtained complete remission (50%). One patient with AML and the patient with CMLBC achieved partial remission. ALL patient failed to obtain remission. Median duration of remission was 4.5 (2-10) months. All patients had severe myelosuppression. Nausea, stomatitis, diarrhea and hepatic dysfunction were the most frequent non hematologic toxicities with similar frequencies in both groups. We conclude that a high rate of remission can be achieved with MITOX + ETOP or MITOX + HD ARA-C combinations in refractory and early relapsed adult acute leukemias with few toxicities under adequate support. In larger groups a clear distinction can be made between these two therapeutic modalities.