Thirty adult patients with relapsing or refractory acute leukemia were treated with mitoxantrone 10 mg/m2 daily by 20-min intravenous infusion for 5 days and cytosine arabinoside (Ara-C) 200 mg/m2 daily by continuous infusion for 5 days. Complete remission was obtained in 9 of 15 patients (60%) with acute myeloblastic leukemia (AML), with a mean duration of 6 months (range 2-12 months). Among 15 patients with acute lymphoblastic leukemia (ALL), complete remission was obtained in 5 patients (33.3%), with a mean duration of 2 months. Partial remission was achieved in 2 patients with AML and 1 patient with ALL. Myelosuppression developed in all patients following chemotherapy. Nonhematologic side effects consisted of nausea, vomiting, mild alopecia, stomatitis and transient hepatic dysfunction. No cardiopulmonary toxicity or neurotoxicity was observed. Our therapeutic responses are similar to those obtained with high-dose Ara-C and mitoxantrone but with less toxicity.