Background and Design.- Intensive sequential chemotherapy with mitoxantrone 12 mg/m2/d on days 1 through 3;. etoposide 200 mg/m2/d as a con¬tinuous infusion on days 8 through 10, cytarabine (Ara-C) 500 mg/m2/d as a continuous infusion on days 1 through 3 and 8 through 10 was administe¬red to 13 patients aged less than 60 years (median 37, range 19-58) with previously treated acute non-lymphoblastic leukemia (ANLL). Results.- Five patients had refractory ANLL (no response to prior therapy), one patient had early first relapse, four patients had late first relapse, three pa¬tients had second relapse. Forty six percent (6 pati¬ents) of the patients achieved complete remission, fif¬teen percent did not respond to therapy and five di¬ed from therapy-related toxicity. Median duration of aplasia was 28 days. Non-hematological WHO grade 3 or more toxicity included infections (46%) in 6 patients, vomiting (30.7%), mucositis (53.8%), diarr¬hea (30.8%), skin rash (7.7%), clinical bleeding (30.8%), cardiac toxicity (7.7%), neurotoxicity (23.1%). Median disease-free survival was 215 days. One patient is alive at 825 days. Conclusion.- These results, when combined with other studies concerning this chemotherapy protocol and keeping in mind the rate of increased toxicity,