AMSA was evaluated in the treatment of 109 adults with previously treated acute leukemia. Of the 102 evaluable patients, 82 had AML, 17 ALL, and 3 CML in blastic phase. A number of different dose schedules of AMSA were explored, and we conclude that the optimum dose of AMSA for remission induction in acute leukemia is 120 mg/sq m/day for 5 days. Complete remissions were observed in 23 (28%) patients with AML and in 1 patient with ALL. Patients who achieved complete remission were maintained on AMSA using a dose of 30–40 mg/sq m/day for 5 days repeated at 4-wk intervals. The median duration of complete remission was 12 wk (3–59 wk), and the responders survived significantly longer than the failures (27 wk versus 8 wk, p = 0.002). The side effects associated with AMSA therapy included mild nausea and vomiting, stomatitis, diarrhea, phlebitis, alopecia, and myelosuppression-related infections. Our results indicate that AMSA is a useful new antileukemic agent for the treatment of relapsed acute leukemia and appears to have activity comparable to that of the currently available drugs, such as cytarabine and the anthracycline antibiotics.