Development of the mucosal immune system was examined in mice with partial loss of expression of ICAM-1 or CD18. Profound effects on Peyer's patch (PP), lamina propria (LP), and intraepithelial lymphocyte (IEL) T cell populations were observed in mutant mice. Normal expression of CD18 integrins and ICAM-1 was essential for development of the CD8(alpha beta) TCR(alpha beta)LP and IEL compartment and for the generation of normal PP lymphocyte populations. The partial loss of CD8(alpha beta) IEL correlated with the loss of TCR(alpha beta) IEL-mediated lytic activity. The presence of a subset of Thy1+TCR(gamma delta)IEL was also dependent on CD18 integrins and ICAM-1. Both the lytic activity and the expression of CD11c by TCR(gamma delta)IEL were up-regulated in the presence of TCR(alpha beta) T cells. Analysis of bone marrow chimeras demonstrated that a bone marrow-derived ICAM-1+ accessory cell was involved in the generation of some TCR(alpha beta) IEL. These results demonstrated that ICAM-1 and beta2 integrins were required for establishment of a normal intestinal immune system.