In vivo ultraviolet (UV) exposure of human skin abrogates the antigen-presenting function of T6+ DR+ Langerhans cells and induces the appearance of antigen-presenting T6− DR+ epidermal melanophages. UV-exposed epidermal cells containing T6− DR + epidermal antigen-presenting cells, in contrast to unexposed epidermal cells containing T6+ DR+ Langerhans cells, potently activate autoreactive regulatory T cells in the absence of exogenous antigens. Autoreactive T cells may be important for regulation of other immune responses such as those which occur in photosensitive lupus erythematosus and in immune surveillance of UV-induced skin cancers. It is therefore imperative to determine the factors that govern their appearance in the skin. It was found that UVB and UVC, but not UVA, induced a dose-dependent appearance of T6− DR + epidermal melanophages. The optimal time of appearance was 2 or 3 days after UVB and UVC exposure. In contrast, UVA was a poor inducer of T6− DR+ cells at all doses and all time points tested. Although UVA was a poor inducer of T6− DR-+ epidermal cells, UVA radiation resulted in depletion of T6+ DR+ Langerhans cells from the epidermis, as did UVB and UVC radiation. This differential effect of UV wave bands on the immunocompetent cells in human skin may be related to the greater potential of UVB exposure to induce skin cancers and to exacerbate systemic lupus erythematosus.