Eighty-eight patients have now been admitted to the primary protocol for the treatment of non-Hodgkin's lymphoma, and the goals of this protocol, namely, to define different prognostic groups within this broad category of patients have largely been achieved. Utilizing a CHOP - high dose methotrexate regimen, the results in lymphoblastic lymphoma without marrow involvement and patients with entirely resected intraabdominal undifferentiated lymphoma or localized disease have been excellent (currently 82% and 90% disease-free survival). Among the remaining patients the most important prognostic feature is bone marrow involvement. These findings have been utilized in the design of protocols in which treatment is tailored to prognostic groups. Overall, the reults of the present protocol show a 15% improvement in terms of disease-free survival over the two previous protocols used in the Pediatric Branch, when the previous results are combined (justified on the basis of a previous multiinstitutional study which showed no difference in outcome between these protocols). The results of 77-04-02 which includes IT therapy also appear to be improved compared to results prior to the introduction of CNS prophylactic IT therapy. Two new protocols have been activated. One is for patients with extensive undifferentiated lymphomas and is based on protocol 77-04. The protocol is more intensive but specifies a much shorter total treatment duration (6 cycles). The second protocol is a new combination (ifosfamide, VP16 and high dose ara-C) which is being evaluated in relapsed patients prior to its possible incorporation into a treatment strategy for high risk patient.