Human skin equivalents composed of keratinocytes cultured on a lattice constituted of human fibroblasts embedded in type I collagen were grafted onto the nude mouse. It is demonstrated, by indirect immunofluorescence and electron microscopy, that, after grafting, mouse Langerhans cells migrate into the human epidermis. Human Langerhans cells are not present in this system. In split-thickness human skin grafts, at long periods (5 and 12 months) after transplantation, a progressive migration of murine Ia(+) cells in the human epidermis and the presence of human Langerhans cells were shown by indirect immunofluorescence. Creation of a wound at the center of the grafted human skin and identification of the Langerhans cell origin shows a repopulation with human Langerhans cells provided the injury was performed early (2 months) after grafting. Injury at a later stage (5 months) resulted in presence of both human and murine Langerhans cells. These observations show 1) that, after grafting of "reconstructed" human skin or of split-thickness human skin onto nude mice, mouse Langerhans cells migrate into the grafted human epidermis; and 2) that the Langerhans cells repopulating a healing grafted epidermis devoid of Langerhans cells derived from the non-injured surrounding epidermis. The present work thus shows that besides bone marrow, lymph nodes, or/and spleen, surrounding cutaneous regions can also serve as sources of Langerhans cells.