Lymphocytes and dendritic cells (DCs) are critical for immune responses, yet how they develop from pluripotenl hematopoietic stem cells is poorly defined. In humans and mice, it is possible to isolate phenotypically defined subsets of bone marrow (BM) cells that represent intermediate progenitors without long-term repopu-lating characteristics but with specific lineage differentiation properties. For instance, murine BM CD34+ CD45RA+ cells are progenitors for B and T lymphocytes with no in vivo repppulation activity. In human BM, a small subset (5%) of cells having the phenotype CD34+ Lin- CD10+ CD45RA+ CD38+ Thy-1- c-kit represents a new class of hematopoietic progenitor cells that gives rise to lymphocytes [T, B, and natural killer (NK) cells] and to DCs but does not produce myeloid or erythroid cells. The identification of such progenitor cells provides the opportunity to define the differentiation and growth requirements for the production of lymphocytes and DCs. Genes involved in lineage specification can also be studied. Altogether, these studies have fundamental implications for understanding the biology of pivotal lineages of immune cells. This understanding could be used to treat a variety of immunodeficiencies and to design novel immunotherapies particularly in the context of hematopoietic cell transplantation.