Sixty-two adults with previously treated acute leukemia were treated with 4'-(9-acridinylamino) methanesulfon-m-anisidide (AMSA) with a total dose of 150 mg to 1320 mg/m2 of body surface area given over 3 to 14 days intravenously. Of the 56 patients who received an adequate trial, 13 achieved a complete remission and six had a partial remission. The best therapeutic results were observed when AMSA was used at a dose level of 75 to 90 mg/m2 per day for 7 days, which resulted in nine complete remissions among 30 patients. Eleven of 38 patients with myeloblastic leukemia achieved complete remission, and three of 13 with lymphoblastic disease achieved partial remission. Complete remissions were observed in nine of 39 patients who were refractory to cytarabine and anthracyclines, indicating a lack of cross-resistance between these drugs and AMSA. The median duration of remission was 12 weeks, and the median survival of responders was 28.5 weeks. The major toxicity of AMSA therapy was severe myelosuppression resulting in frequent infections during induction therapy. Our results indicate that AMSA has significant activity against refractory adult acute leukemia and deserves further evaluation.