The architecture of the thymus of mice that congenitally fail to express the alpha beta T-cell receptor (TCR alpha beta) has been examined by immunohistology. In these mice, a defined mutation was introduced into the TCR alpha gene by homologous recombination. By using antibodies specific for cortical or medullary epithelium and for major histocompatibility complex antigens, the network of cortical epithelium in these mice was shown to be essentially unaltered in comparison with that of normal mice. In contrast, the thymic medulla was considerably reduced in size. This analysis shows that expression of the alpha beta TCR but not the gamma delta TCR is obligatory for establishing the thymic medulla and suggests that the growth of medullary epithelial cells may require contact with TCR alpha beta-expressing cells.