Epidermal Langerhans cells (LC) play pivotal roles in the induction of cutaneous immune responses. Encounter with antigen in the skin, or other stimuli, cause the mobilization of LC and their migration, via afferent lymphatics, to draining lymph nodes where they localize within the paracortex. During their movement from the skin LC acquire the characteristics of immunostimulatory dendritic cells (DC) such that the antigen-bearing cells which accumulate in lymph nodes are able to provoke specific T-lymphocyte responses. Epidermal cytokines initiate and regulate LC migration (and maturation), of particular importance being interleukin-1beta and tumour necrosis factor-alpha. Collectively, these cytokines, together with relevant chemokine receptor-ligand interactions, effect the liberation of LC from the epidermis and their directed movement to, and localization within, peripheral lymph nodes. Described here are the phenotypic changes induced during the activation of LC and the mechanisms through which their migration is regulated.