Twenty-nine consecutive children with untreated non-Hodgkin's malignant lymphoma were admitted to Istituto Nazionale Tumori of Milan during the period from 1974 through 1976 and underwent treatment with chemotherapeutic regimens consisting of Adriamycin, Cytoxan, vincristine, and prednisone (two month induction phase) and 6-mercaptopurine, methotrexate, Adriamycin, vincristine, and prednisone (maintenance phase). Each patient, regardless of clinical stage of histologic subgroup, was given the same chemotherapy. The complete response rate was 66%. Due to the high incidence of recurrence of the initial bulky lymphomatous mass and of spread to the central nervous system (CNS), local radiotherapy was given to ten children and CNS prophylaxis (brain radiotherapy + intrathecal methotrexate) to 11 children. After a follow-up period in excess of 40 months, there were five disease-free survivors (17%). Each patient who had a relapse died from the disease. The main reason for first treatment failure was relapse at the level of the primary bulky tumor site or spread to the CNS. This type of CNS prophylaxis did not prevent relapse at this site.