From June 1976 to May 1980, 25 previously untreated children with non-Hodgkin's lymphoma (NHL) were studied and treated with a protocol modified from the one (LSA2L2) proposed by Wollner [8]. Stage III and IV had, in addition, prophylactic treatment of the central nervous system (CNS) with cranial irradiation (2,400 rad plus intrathecal methotrexate). The complete remission rate is 96%. Of these patients, 76% are disease free surviving after a median observation time of nearly two years. The disease-free actuarial survival is 100% for 6 children with Stage I-II disease and 68% for 19 Stage III-IV children after median observations times respectively 25 + and 19 + months. None of the 19 high-risk patients developed CNS disease after prophylactic treatment. Mediastinal involvement and leukemia conversion at diagnosis were not unfavorable prognostic factors, but primary skeletal or subcutaneous disease and Burkitt-tupe histology were ominous features in patients treated by this regimen. It is concluded that good results are obtained when an aggressive multimodal and multiple drug regimen like the LSA2-L2 is coupled with CNS prophylaxis and is used assiduously to maintain complete remission during the first 12 months of treatment.