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Langerhans cells (LC) are bone marrow-derived, la⁺, CD1⁺, CD4⁺, ATPase⁺ dendritic antigen-presenting cells within the human epidermis. Since the CD4 molecule has been implicated as a receptor structure for HTLV-III/LAV (human T-cell leukemia virus/lymphadenopathy-associated virus), we asked whether LC from HTLV-III/LAV-seropositive individuals display signs of HTLV-III/LAV infection. In skin biopsies from 7/40 HTLV-III/LAV-infected persons (1 asymptomatic carrier, 2 patients with acquired immunodeficiency syndrome (AIDS)-related complex and 4 patients with AIDS), LC were the only epidermal cells to react with a monoclonal antibody specific for the HTLV-III core protein p17. A varying percentage of p17⁺ LC were morphologically altered with blunt dendrites and poorly demarcated cellular contours. In one of these biopsies, the presence of LC-associated viral particles characteristic of HTLV-III/LAV as …