The early stages of lymphoid cell formation were studied by testing the differentiative potential of phenotypically defined subsets of CD34+ bone marrow cells. A subpopulation of CD34+ Lin-CD45RA+ cells expressing CD10 was Isolated by flow cytometry. Such cells are CD38+, HLA-DR+, do not express significant levels of Thy-l and c-kit, lacketythroid, myeloid, megakaryocytic potential, and give rise only to lymphoid T, B, natural killer (NK), and dendrltic cells (DC) in kinetics and titration experiments. Limiting dilution analysis demonstrates the existence of multipotential BINKIDC progenitor clones in the CD34h’LinCDlO+ adult bone marrow cell population. Thus, nonprimitive progenitors for lymphoid cells and for DCs can be distinct from those of myeloid, megakaryocytic, and erythrold cells, implying that the DC lineage is developmentally more closely related to the lymphoid lineage than to the myeloid lineage. This study provides new insights into the organization and development of the human lympho-hematopoietic system.