Dendritic cells (DCs) are potent antigen-presenting cells with a pivotal role in antigen-specific immune responses. Here, we found that the helix-loop-helix transcription factor Id2 is up-regulated during DC development in vitro and crucial for the development of distinct DC subsets in vivo. Id2^−/− mice lack Langerhans cells (LCs), the cutaneous contingent of DCs, and the splenic CD8α⁺ DC subset is markedly reduced. Mice deficient for transforming growth factor (TGF)-β also lack LCs, and we demonstrate here that, in DCs, TGF-β induces Id2 expression. We also show that Id2 represses B cell genes in DCs. These findings reveal a TGF-β–Id2 signaling pathway in DCs and suggest a mechanism by which Id2 affects the lineage choice of B cell and DC progenitors.