Listeria monocytogenes is an intracellular bacterium that causes systemic infections after traversing the intestinal mucosa, Clearance of infection and long term protective immunity are mediated by L, monocytogenes-specific CDS T lymphocytes, In this report, we characterize the murine CD8 T cell response in the lamina propria and intestinal epithelium after enteric L, monocytogenes infection. We find that the frequency of MHC class Ia-restricted, L. monocytogenes-specific T cells is similar to4- to 5-fold greater in the lamina propria than in the spleen of mice after oral or i.v. infection. Although the kinetics of T cell expansion and contraction are similar in spleen, lamina propria, and intestinal epithelium, high frequencies of Ag-specific T cells are detected only in the lamina propria 1 mo after infection. In contrast to MHC class la-restricted T cells, the frequency of H2-M3-restricted, L, monocytogenes-specific T cells is decreased in the intestinal mucosa relative to that found in the spleen. In addition to this disparity, we find that MWC class Ia-restricted CD8 T cells specific for a dominant L, monocytogenes epitope have different TCR V beta repertoires in the spleen and intestinal mucosa of individual mice. These findings indicate that the intestinal mucosa is a depot where L, monocytogenes-specific effector CD8 T cells accumulate during and after infection irrespective of immunization route. Furthermore, our results demonstrate that CD8 T cell populations in these two sites, although overlapping in Ag specificity, are distinct in terms of their repertoire.