Epithelium-lining macrophages are spindle-shaped cells which line the epidermis and hair follicles. We studied the distribution and phenotype of this hitherto neglected member of the dermal monocyte/macrophage system in 25 lesional psoriatic, and five normal skin biopsies. Epithelium-lining macrophages were inconspicuous in normal skin, whereas their number was increased in almost two-thirds of psoriatic cases; in nine out of 25 lesional skin biopsies, these flattened cells formed an almost continuous single-cell row at the dermo-epidermal junction. Immunophenotyping revealed that these cells expressed the leucocyte common antigen CD45, and the macrophage markers CD14, CD36 and CD4, but not CD11b. Epithelium-lining macrophages strongly expressed HLA-DR-antigens and CD11a, but lacked the Langerhans cell marker CD1, and CD34. The dermal dendrocyte marker factor XIIIa was expressed in only a minority of these cells. It is concluded that epithelium-lining macrophages represent a separate subset of dermal monocytes/macrophages with a distinct tissue localization and immunophenotype. Their restricted distribution and close association with the epidermis may suggest a role in the regulation of epidermal growth. Alternatively, the expression of several immune-associated molecules may indicate that epithelium-lining macrophages are involved in the antigen-dependent or -independent activation of T cells.