The concept that a pluripotent stem cell exists and has the capacity eventually to give rise to mature B and T cells is uncontestable. However, the precise development relationship between pluripotent stem cells and the earliest stages of B-cell and T-cell development are still obscure. Patterns of gene expression are being identified that characterize normal B-cell and T-cell precursors, and the regulatory variables that influence self-renewal and differentiation of these cells. These are important studies because childhood lymphoblastic leukemia almost always manifests a cellular phenotype consonant with an immature lymphoid cell. A comprehensive understanding of the etiology of acute lymphoblastic leukemia will likely be hastened by a more thorough understanding of normal lymphopoiesis. This knowledge will complement the large data base that currently characterizes lymphoblastic leukemia in children.