After hapten application, epidermal Langerhans cells migrate into the regional lymph nodes through dermal lymphatics. Recently, we have demonstrated that some of them take the phenotypic and functional characteristics similar to those of in vitro cultured Langerhans cells, before disappearing from the epidermis. To analyze the mechanisms underlying the migration of Langerhans cells, we studied the expression of several adhesion molecules on freshly isolated LC and cultured LC. Pgp-1 (CD44), intercellular adhesion molecule 1, and alpha4 integrin were strongly expressed on cultured Langerhans cells. Among them, only alpha4 integrin was strongly up-regulated by cultured Langerhans cells, because its expression by freshly isolated Langerhans cells was very weak. This up-regulation of alpha4 integrin was also observed on in vivo activated Langerhans cells in the epidermis and draining lymph nodes after hapten application. These data suggest a possible role played by VLA-4 in the migration of Langerhans cells from the epidermis into the regional lymph nodes after hapten application.