The activation of CD8 T cells was studied using transgenic mice expressing an MHC class I-restricted OVA-specific TCR (OT-I). Immunization of OT-I mice resulted in activation of lymph node T cells and up-regulation of expression of B220, CD11a, and CD44 and caused a preferential loss of mucosal-type T cells from the periphery. Immunization induced dramatic changes in intestinal lymphocytes, including the appearance of a CD11a high population that resembled peripheral T cells and induced a primary cytolytic response. Activation of adoptively transferred OT-I cells induced migration of CD8 T cells into the lamina propria and intraepithelial lymphocyte compartments. The results suggest that Ag presentation in the intestinal epithelium occurs, and that CD8 cells activated in the periphery can readily enter the mucosa during an ongoing immune response.