SUMMARY The influence of low-dose, long-term ultraviolet B (UVB) light exposure on HLA class Il-positive human epidermal Langerhans cells (LC) was studied using a sensitive immunoelectron microscopic technique for the ultrastructural assessment of HLA class II expression on LC and for quantification of these cells in situ. Six healthy Caucasian volunteers participated in the experiments and received thrice weekly UVB treatments for 4 weeks. The initial dose ranged from 30 to 50mJ'cnv and the total dose from 600 to 3500 mJ/cm2, depending on skin type. Suction blisters and biopsies were obtained before the start of the UVB protocol and 48 h after the last UVB irradiation, and processed for the mixed epidermal cell-lymphocyte reaction (MECLR) and electromicroscopy, respectively, The MECLR was used as a measure of the immune response. The distribution of HLA class 11 molecules on LC was studied by incubating ultrathin cryosections of human skin tissue with an anti-HLA class II MoAb that was conjugated to 10 nm colloidal gold. Furthermore the number of LC was assessed ultrastructurally, when they could be recognized by their unique cytoplasmic organdie, the Birbeck granule (BG). The UVB protocol that was employed caused a marked suppression of the MECLR responses. This UVB-induced reduction of the immune response was not paralleled by changes in HLA class II expression on LC. nor in the number of epidermal LC. These findings are further support for our hypothesis that UVB-induced immune suppression in the skin is not due to a depletion of local LC.