Adults (52) treated previously for either acute leukemia (43 patients) or blastic-phase chronic myelogenous leukemia (9 patients) received 4-demethoxydaunorubicin (20-45 mg/sq m) i.v. over 2-3 days. Three of the 10 patients with acute lymphocytic leukemia achieved a complete remission (CR) lasting 5-7 wk. Five of the 28 patients with acute nonlymphocytic leukemia achieved a CR lasting 5-80 wk. All remissions were induced with 1 course of treatment with a median time to CR of 28 days (range, 22-40 days). None of the patients with blastic chronic myelogenous leukemia or secondary leukemia achieved a CR. The drug was well tolerated; mucositis (36%), nausea and vomiting (35%) and hepatic dysfunction (26%) were the most common side effects. Pharmacokinetic observations on 5 patients demonstrated multiphasic clearance of 4-demethoxydaunorubicin and extensive formation and prolonged retention of 4-demethoxy-13-hydroxydaunorubicin; that metabolite accumulated in plasma on repeated daily dosing. 4-Demethoxydaunorubicin has sufficient antileukemic activity in both acute lymphocytic leukemia and acute nonlymphocytic leukemia to warrant a prospective comparison, in combination regimens, against the conventional anthracyclines, daunorubicin and/or doxorubicin.