In order to reduce the incidence of severe complications noted with regimens containing high-dose cytarabine (HD ARA-C), wer used a combination of mitoxantrone (MTZ) in optimal dosage (12 mg/m2/day for 5 days) and cytarabine in intermediate dosage (1 g/m2 twice daily for 3 or 5 days). Thirty patients aged 2 to 65 years (median 51) with acute myeloid leukemia (AML), either refractory (8 patients), in first relapse (20 patients) or chemoinduced (2 patients), received this program. Seventeen (57%) achieved complete remission (CR). The main prognostic factor was the previous use of HD ARA-C (21% CR for patients previously treated with HD ARA-C versus 87% for patients treated with conventional doses: P less than 0.001). Mucositis was the most significant extrahematologic side-effect. There was no severe cerebellar toxicity. Two patients had transient congestive cardiac failure. This regimen is effective and relatively well tolerated in heavily pretreated patients. It can be used either as induction or consolidation therapy in AML.