About 85% of children with ALL have leukemic blasts that express cell membrane antigens associated with B-cell lineage, although few are surface immunoglobulin positive. Patients differ from children with ALL of T-cell lineage in that they tend to be younger, less predominantly male, and less likely to have a mediastinal mass or CNS leukemia at diagnosis, and they have a lower leukocyte count. Leukemic blasts from these children are more likely to be hyperdiploid. However, B cell-lineage ALL is not homogeneous either. It includes infants, children, and adolescents; it includes patients with leukemic blasts that either express or fail to express CD10, CD24, and cytoplasmic immunoglobulin. B cell-lineage ALL includes patients with blasts showing hyperdiploidy and patients with blasts with translocations such as t(4;11), t(1;19), and t(9;22). In general, outcome for patients with B cell-lineage ALL is superior to the outcome of those with T cell-lineage ALL in univariate analysis. However, when comparisons are stratified by age and leukocyte count, any apparent prognostic advantage for children with B cell-lineage ALL is diminished. The addition of effective CNS prophylaxis to effective systemic chemotherapy made cure a reality for about one half of children with ALL. Subsequent work has made it possible to omit cranial irradiation and its sequelae for most children with ALL. At least three regimens have offered an unambiguous improvement over the original St. Jude prophylactic CNS therapy regimen. These regimens are the BFM 76/79 regimen, the New York regimen, and the Dana-Farber regimen. Cure appears possible for 70% of children. These regimens differ markedly in detail, but appear to benefit similar subsets of patients. Identification of their critical therapeutic elements is one challenge for the future. A second challenge is the early identification of patients likely to do poorly on these effective regimens, whether by age under 1 year, specific blast morphology, cytochemical findings, immunophenotype, cytogenetic findings, drug pharmacokinetic features, or early response to antileukemic therapy. The third challenge is continued awareness of the acute morbidity of therapy and its impact on the lives of children and their families, together with a heightened vigilance for likely long-term sequelae. Most children with lymphoblastic leukemia in the United States are referred to cancer treatment centers for the initiation of therapy. Over one half of the children who are diagnosed participate in formal clinical trials.(ABSTRACT TRUNCATED AT 400 WORDS)