Amsacrine (AMSA) has been shown to be an effective therapeutic agent in the treatment of adult acute nonlymphocytic leukemia (ANLL). The Eastern Cooperative Oncology Group studied the efficacy and toxicity of high-dose amsacrine (200 mg/m2/day for 5 days) in 38 adult patients with refractory and relapsed ANLL. The complete remission rate was low (8%). This dose level of amsacrine caused severe mucositis in 24% of patients and marked liver function abnormalities in 11%. Seizures did not occur, and two reversible cardiac events were not clearly attributable to amsacrine administration. Escalation of amsacrine beyond currently recommended total doses of 600-750 mg/m2 is unlikely to be of benefit.