To characterize thymic epithelial cells of SCID (severe combined immunodeficiency) mice in comparison with those of Balb C mice, we did an immunohistochemical study using cortical and medullary epithelial cell specific monoclonal antibodies (MoAbs), Th-3 and Th-4, as well as gel electrophoresis and immunoblotting. The thymi of SCID mice were composed of epithelial cells and a few lymphocytes. Most epithelial cells were immunostained diffusely with Th-3, which indicated that they might be "cortical-type" epithelial cells. There were a few clusters of stellate cells with dendritic processes which were negative with Th-3 but stained strongly with Th-4. Cortical type epithelial cells and most of the Th-4 reacting cells were strongly immunostained with cytokeratin antibody MNF116. By immunoblotting, cytokeratin polypeptides No. 10 and 18 were detected in both SCID and Balb C mice; however, the relative amounts of each cytokeratin polypeptides were different. With immunohistochemical and immunoblotting results, we conclude; 1) Th-3 and Th-4 are reliable markers for cortical and medullary thymic epithelial cells in SCID mice; 2) disorganization of cells thymic structure is mostly due to maldevelopment of medullary epithelial and T lymphocytes; and 3) the composition of cytokeratin subfamilies of SCID mice thymi may represent a phenotypic marker of the maldevelopment of medullary epithelial cells.