Tissue-selective trafficking of memory and effector T and B lymphocytes is mediated by unique combinations of adhesion molecules and chemokines. The discovery of several related epithelial-expressed chemokines (TECK/CCL25 in small intestine, CTACK/CCL27 in skin, and MEC/CCL28 in diverse mucosal sites) now highlights an important role for epithelial cells in controlling homeostatic lymphocyte trafficking, including the localization of cutaneous and intestinal memory T cells, and of IgA plasma cells. Constitutively expressed epithelial chemokines may help determine the character of local immune responses and contribute to the systemic organization of the immune system.