One hundred thirty-seven children with previously untreated acute lymphoblastic leukemia were entered into a new program that included intermittent combination chemotherapy featuring Adriamycin. Remission induction was initially randomized to vincristine and prednisone with or without an anthracycline. All children received asparaginase consolidation and central nervous system prophylaxis with cranial irradiation and intrathecal methotrexate. There were no primary failures of CNS prophylaxis. Complications were primarily infectious. Clinical evidence of cardiotoxicity and leukoencephalopathy were not observed. The time to enter complete remission and the presence of an anterior mediastinal mass at diagnosis were found to be statistically significant adverse prognostic factors, whereas presenting age and white blood count were not. With a median follow-up of 26 mo, and using life plot analysis, 65% of the children have remianed in continuous complete remission.