Whether a cell committed to the B-cell lineage finally succeeds in entering the pool of newly-generated B cells depends on the Ig gene rearrangements it acquires during its differentiation. During the past decade, the immunoglobulin (Ig) gene rearrangement program has heen analyzed with the help of Abelson virus-transformed pre-B cell lines that spontaneously undergo rearrangement of Ig loci in vitro. Based on these studies, the following mode! of B-cell development was formulated (Alt et al. 1984, 1987): B-cell precursors first assemble D^ JH rearrangements. As soon as a productive VH-* DHJH joint is made, IgH rearrangement ceases and L (light) chain loci are rearranged. For IgL gene rearrangement again an order has been postulated: V^ J^. joints were suggested to be generated prior to V^ J; joints. Once a L chain is expressed, the cell displays surface immunoglobulin (sig) and further Ig gene rearrangements are stopped. We have used gene-targeted mice to analyze the in vivo requirements for B-cell differentiation. While B-cell development in mice lacking membrane-bound/j.-lnstitute for Genetics, University of Cologne, Weyertal 121, D-50931 Cologne, FRG. RR Hardy; Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, PA 19! 11, USA.