Transcription factors with a basic helix-loop-helix (HLH) moth have been shown to be crucial for various cell differentiation processes during development of multicellular organisms(1), Id proteins inhibit the functions of these transcription factors in a dominant-negative manner by suppressing their heterodimerization partners through the HLH domains(2-4). Members of the Id family also promote cell proliferation(4,5), implying a role in the control of cell differentiation. Here we show that Id2 is indispensable for normal development of mice, Id2(-/-) mice lack lymph nodes and Peyer＇s patches. However, their splenic architecture is normal, exhibiting T-cell and B-cell compartments and distinct germinal centres, The cell population that produces lymphotoxins, essential factors for the development of secondary lymphoid organs(6-11), is barely detectable in the Id2(-/-) intestine, Furthermore, the null mutants show a greatly reduced population of natural killer (NK) cells, which is due to an intrinsic defect in NK-cell precursors, Our results indicate that Id2 has an essential role in the generation of peripheral lymphoid organs and NK cells.