IL-7 signaling is required for V(D)J recombination at the TCRgamma locus. We have recently reported that IL-7 controls chromatin accessibility for RAG-mediated cleavage. Inhibition of histone deacetylase substituted for the IL-7 signal, indicating a role for histone acetylation in altering chromatin accessibility. We found a greatly reduced histone 3 and histone 4 acetylation level in IL-7Ralpha(-/-) thymocytes in comparison with RAG(-/-) thymocytes or fetal thymocytes. Sterile transcripts, indicating an open chromatin configuration, were suppressed in IL-7Ralpha(-/-) and IL-7(-/-)RAG(-/-) thymocytes. Moreover, exogenously added IL-7 induced sterile transcripts from the TCRgamma constant region in cultured thymocytes from IL-7(-/-)RAG(-/-) mice. This induction correlated with increased histone acetylation at the J-promoter and C-enhancer regulatory elements at the TCRgamma locus. These results suggest that IL-7 regulates chromatin accessibility for V(D)J recombination by specifically altering histone acetylation within the TCRgamma locus.