Dendritic cells are the major antigen-presenting cells, especially for naive T lymphocytes; it is conceivable therefore that their absence or dysfunction may induce an immune deficiency (ID). Few data are available, however, concerning dendritic cells in human primary ID. Langerhans' cells (LC) are intraepidermal dendritic cells which express specific markers and may therefore be studied by immunohistochemistry on paraffin-embedded skin samples. Skin samples of nine children with primary ID were studied and compared with five age-matched controls. LC were present within the epidermis of two children with X-linked severe combined ID, a condition related to the lack of the common gamma-chain of interleukin-2 (IL-2), IL-4, IL-7, IL-9, and IL-15 receptors. LC were also present in skin samples of a child with Omenn syndrome and in three children with combined ID. By contrast, no LC were detected in the skin samples of two children with alymphocytosis and of a child with reticular dysgenesis, a condition characterized by the absence of peripheral blood leukocytes.