Langerhans cells, important participants in the cutaneous cellular immune response, are markedly diminished in skin of patients undergoing allogeneic bone marrow transplantation during the first 4 weeks after this procedure. To determine the mechanism responsible for the subsequent repopulation of these cells, the authors studied the immunophenotypic and morphologic profiles of sequential skin biopsies during the posttransplantation period. Cells with surface antigens of monocytes/macrophages within the superficial dermis were gradually replaced by dermal and epidermal dendritic cells exhibiting coexpression of monocyte/macrophage and Langerhans cell surface antigens. Ultrastructural examination revealed that many of these cells contained both prominent phagolysosomes and Birbeck granules. Antigenically and structurally mature Langerhans cells were observed within the epidermis by the end of the second month after transplantation. Phenotypic transformation of phagocytic dermal macrophages to Langerhans cells appears to represent a mechanism for repopulation of Langerhans cells during the period of immunologic reconstitution in this patient population.