The integrin α4β7 binds to MAdCAM-1 and contributes to homing of lymphocytes to gut and other mucosal tissues. In humans, the α4β7hi subset of circulating memory cellsappears to have been primed in mucosal tissues. The factors that determine whether α4β7lo naive cells become α4βhi or α4β7– cells upon differentiation are poorly understood but could include an influence of the activating antigen-presenting cell. To address this point, the induction of α4β7 following activation of mouse cells with theAPC-dependent stimulus soluble anti-CD3 has been examined. Almost all mouse T cells freshly isolated from mesenteric lymph nodes (MLN) and peripheral (PLN; axillary, brachial and inguinal) lymph nodes stained only weakly for α4β7 but a subpopulation became α4β7hi upon activation with anti-CD3 in a cell cycle- and accessory cell-dependent manner. A small proportion (approximately 1.5 %) of the starting cells gave rise to α4β7hi cells after culture. A higher proportion of α4β7hi cells were generated in MLN than PLN cultures. Peyer's patch cultures gave intermediate values. In crossover experiments, MLN dendritic cells (DC) induced higher proportions and numbers of α4β7hi cells than PLN DC irrespective of the source of T cells. Therefore, in addition to their other immunoregulatory roles, DC have the potential to shape immune responses by influencing the homing of the lymphocytes they activate.