Abstract ICAM-1 and P-selectin are adhesion molecules that regulate leukocyte migration, extravasation to inflammatory sites, and other immune cell interactions. T cell-mediated resistance against acute infection with Listeria monocytogenes and chronic infection with Mycobacterium bovis Calmette-Guérin bacillus was investigated in mutant mice lacking P-selectin and/or ICAM-1. Mice deficient in P-selectin (Psel−/−), ICAM-1 (ICAM−/−), or the combination of both (Psel−/− × ICAM−/−) showed normal bacterial clearance, comparable delayed-type hypersensitivity reactions, and equivalent memory T cell responses. Additionally, the distribution of αβ vs γδ T lymphocyte populations was examined. Normal lymphocyte distributions were noted in thymus, spleen, and blood, whereas mutant mice showed marked alterations in the intestinal intraepithelial (i-IEL) and lamina propria lymphocytes. Differences in i-IEL populations were reflected functionally by differential lytic activities and cytokine productions of i-IEL populations from mutant mice. Despite these changes within the mucosal immune system of mutant mice, their resistance against oral infection with L. monocytogenes was apparently unimpaired. These findings demonstrate that P-selectin and ICAM-1 are critically involved in the shaping of lymphocyte populations of the gut but have only a minor influence on systemic and regional host defense against intracellular bacteria.