Mitoxantrone was administered as a single iv injection once every 3 weeks to 84 children with advanced acute leukemia and solid tumors in a phase I trial. Dose-limiting granulocytopenia occurred at dosages greater than 18 mg/m2 in children with solid tumors, while hospitalization for febrile episodes occurred in nine of 12 patients with acute leukemia receiving dosages greater than 24 mg/m2. Six children developed evidence of cardiac dysfunction, including three instances of congestive heart failure. No other significant toxicity was noted. Complete responses were seen in one child with neuroblastoma metastatic to bone, one with acute lymphoblastic leukemia, and four with acute nonlymphoblastic leukemia.