There have been no reports on an abundance of CD4- 8- B220+ alphabeta T cells, seen in autoimmune mice carrying the lpr gene (abnormal Fas gene), in any immune organs of normal mice. We herein report, however, that such alphabeta T cells were abundant at intraepithelial sites of the appendix in normal mice. They lacked the expression of NK1.1 Ags (C57BL/6 mice), but had the morphology of granular lymphocytes and contained forbidden T cell clones in the minor lymphocyte-stimulating antigen (Mls) system (C3H/He mice with Mls-1b2a). In other words, many properties of intraepithelial T cells in the appendix resembled those ascribed to abnormal alphabeta T cells, which expand in the lymph nodes and spleen of lpr mice. In the case of lpr mice, CD4- 8- B220+ alphabeta T cells first expanded in the appendix and then extended to other organs. CD4- 8- B220+ alphabeta T cells seemed to originate in situ from c-kit+ stem cells in the appendix. These results suggest that the appendix is one of the primary sites in which CD4- 8- B220+ alphabeta T cells exist, and that these cells carry many primordial properties as prototype T cells.