The basolateral membranes of intestinal M cells are invaginated to form large intraepithelial "pockets" that are populated by specific sub-sets of mucosal leukocytes, including CD4+ T cells, memory and naïve B cells, and occasional dendritic cells. The adhesion molecules involved in leukocyte trafficking and/or retention within this unique immunological niche are unknown. In this study, we used immunofluorescence microscopy and a battery of monoclonal antibodies to identify the adhesion molecules expressed by leukocytes situated within the intracellular pockets of mouse Peyer's patch (PP) M cells. M cell associated leukocytes (MAL) consistently stained positive for integrin alpha4beta7, and integrin LFA-1 (CD11a/CD18), but were rarely positive for L-selectin (CD62L) or the mucosal integrin alphaEbeta7. However, neither the alpha4beta7 ligands MadCAM-1 or VCAM-1, nor the LFA-1 ligand ICAM-1, were detected on M cell basolateral membranes. To determine whether integrins alpha4beta7 or LFA-1 play a functional role leukocyte homing to M cell pockets, we examined M cells in mice deficient in integrin beta7 or CD11a/CD18. Although PP from CD18 or integrin beta7 mice were reduced in number and size as compared to age-matched controls, we identified M cells in both strains of mice. However, mice lacking CD18 (but not integrin beta7) had significantly fewer leukocytes within M cell pockets as compared to control animals, suggesting LFA-1 (but not alpha4beta7) may contribute, in part, to leukocyte trafficking into and/or retention within this unique immunological niche.