Epidermal Langerhans cells (LCs) possess surface markers and functional attributes which identify them as being of macrophage/monocyte lineage, and recent evidence documents their participation in certain immune process which occur in skin. To assess the role of LCs in lupus erythematosus (LE), a disease in which immune system dysfunction predominates, human epidermis from patients with cutaneous LE was studied with 3 LC surface markers: ATPase activity, HLA-DR and OKT-6 antigens. Suction blister top epidermal skin biopsies from patients with 3 clinical types of cutaneous LE exhibited similar features: LCs were less dendritic, they were more irregularly distributed, and they were present in fewer numbers when compared with those in adjacent normal skin. These changes contrasted with those observed in diseases with similar lichenoid histopathological features. LCs appeared increased in number in lichen planus. LCs in skin lesions from one patient with dermatomyositis exhibited similar morphologic alterations, but surface densities and distributions were preserved. Disaggregated epidermal cells from skin lesions of patients with cutaneous LE induced allogeneic lymphocyte proliferation as efficiently as did cells from nonlesional skin, indicating that the morphologic alterations observed were not associated with a decreased alloantigen presenting capacity. These studies have demonstrated that epidermal LC populations in 3 clinical types of cutaneous LE are perturbed in a manner not seen in 2 other lichenoid skin diseases, although these changes were not associated with an altered capacity of such cells to stimulate proliferation by allogeneic lymphocytes.