In order to assess the possible role of lymphoid cells in the development of thymic epithelium, we compared the organization and maturation of thymic epithelium in scid mice lacking T cell receptor (TcR)-positive cells with that in scid mice containing TcR+ cells. Immunohistologic examination revealed that thymi from TcR scid mice were deficient in thymic medullary epithelial cells recognized by the monoclonal antibody ER-TR5, and that the few thymic medullary epithelial cells present were not organized into discrete medullary areas. In contrast, thymi from scid mice containing TcR+ cells possessed ER-TR5+ thymic medullary epithelial cells and these cells were organized normally into discrete medullary regions. Thus, normal organization and maturation of thymic medullary epithelial cells did not occur in the absence of TcR+ cells, but did occur upon introduction of TcR+ cells. We conclude that lympho-stromal cell interactions in the thymus are not unidirectional, and that a symbiotic relationship exists between maturing epithelial cells and developing lymphocytes.