Thymus development and microenvironment organization require stage‐ and site‐specific cross‐talk between thymocyte and stroma. In this study we have used recombinase‐activating gene‐deficient (RAG‐2^{– / –}) mice to analyze regulated gene expression both in thymocytes and stromal cells following injection of anti‐CD3 monoclonal antibodies as inducer of thymus development. We show that IFN‐γ, TNF‐α and lymphotactin are transcriptionally regulated in thymocytes, whereas cytoskeletal keratin 14, IL‐1α and TNF‐α are regulated in the stroma, quantitatively reproducing the variations associated with β selection of thymocytes. In addition, RAG‐2^{– / –} thymus development is associated with entry of epithelial cells into the cell cycle. The histochemical evidence that expanded RAG‐2^{– / –} thymus becomes undistinguishable from wild‐type cortex further suggests that cross‐talk phenomena occurring during β selection of thymocyte are reproduced in this system.