Results are reported on 724 children and adolescents with acute leukemia-lymphoma. One hundred patients had immunologic marker analysis that defined the major phenotypic groups, i.e., T-cell, B-cell (Burkitt), myeloid, and the most frequent form, non-T, non-T "common" or "undifferentiated" acute leukemia. Pre-T, pre-B, and "null" leukemias are included in the latter group. Response to therapy and survival was best in non-T, non-B acute lymphocytic leukemia, intermediate in T-cell disease, and worst in B-cell (Burkitt) disease. Additional factors resulting in decreased survival include elevated peripheral leukocyte count, presence of enlarged nodes, less depression of hemoglobin and platelets, and age greater than 7 years (all associated with 'lymphomatous" disease). Other factors resulting in decreased survival include age under 3 years and depression of serum immunoglobulins. Definition of the heterogeneity of childhood leukemia-lymphoma dictates differing forms of therapy for the various types of these diseases.