Thirty-two patients with heavily pretreated, relapsed acute leukemia were treated with amsacrine (120 mg/m2/day X 5). The 32 patients received a total of 41 courses of therapy, and 31 patients were evaluable for response. There were no complete remissions and only one partial remission (3 months) in an adult patient with acute lymphoblastic leukemia. Toxic effects included myelosuppression (100% of the patients), hyperbilirubinemia (41%), nausea and vomiting (41%), stomatitis (9%), and cardiac dysrhythmia (3%). We conclude that amsacrine as a single agent is not a useful treatment for relapsed, heavily pretreated adult and pediatric acute leukemia.