Id2 is a Gfi-1 target that mediates Gfi-1 function during B-cell and myeloid development. Gfi-1 is a component of the B-cell transcriptional network through Id2 regulation. Repression of Id2 expression by Gfi-1 is required for B-cell development. In Gfi-1–deficient mice, high levels of Id2 expression are observed in B-cell progenitors, which lead to B-cell inhibition. Id2 also mediates Gfi-1 function in myeloid development. In Gfi-1–deficient mice, high levels of Id2 expression are observed in myeloid progenitors, which lead to myeloid hyperplasia and differentiation arrest.