Forty-eight patients with acute myelogenous leukemia (AML) not eligible for anthracycline or mitoxantrone treatment, mostly due to cardiac contraindications, were given aggressive therapy using m-amsacrine (AMSA) in combination with conventional or high-dose cytarabine for remission induction. Twenty-nine patients (60.4%) responded to treatment, and complete remission was attained in 19 (39.6%), partial remission in 4 (8.3%) and death in bone marrow aplasia without detectable blasts in 6 patients (12.5%). Median time to granulocyte recovery was 32 days, median duration of relapse-free survival 199 days. One patient experienced a serious cardiac adverse event; nausea and vomiting were observed in 73%, diarrhea in 44%, and hepatoxicity in 29% of patients. All potentially AMSA-related side effects were fully reversible, and a lethal complication did not occur. It is concluded that combination chemotherapy with AMSA and Ara-C is also effective and tolerable in leukemic patients in whom cardiotoxic drugs are contraindicated.