CZ-1 is a novel sialic acid-dependent epitope of the murine CD45RB molecule which is expressed on cells that proliferate when cultured in IL-2. Because IL-2 appears to be important in the differentiation of NK cells, the authors examined the expression of CZ-1 on immature NK-lineage cells within the bone marrow. All mature NK1.1+ cells as well as their NK1.1- IL-2 responsive precursors were CZ-1+. Furthermore, IL-2 unresponsive transplantable NK progenitor cells expressed CZ-1 also. To examine expression of CZ-1 on other immature lymphoid progenitor cells, CZ-1+ and CZ-1- marrow cells were transplanted into lightly irradiated scid mice. Transfer of CZ-1+ cells resulted in rapid and sustained generation of thymocytes and splenic B cells, whereas CZ-1- cells caused delayed repopulation. This suggested that the slowly repopulating pluripotent stem cells lacked CZ-1. Therefore, expression of CZ-1 on Ly6+ Lin- c-kit+ cells, highly enriched for pluripotent stem cells, was examined. This population appeared to be homogeneously CZ-1dull. Thus, it appears that expression of CZ-1 is developmentally regulated, with differentiation associated with increased expression. Since CZ-1 is expressed on a protein tyrosine phosphatase, it is likely that this molecule regulates differentiation of NK and other lymphoid cells.