Dendritic cells are considered to be the most potent antigen-presenting cells, and CD83 is expressed at a high level in immunocompetent, activated and mature dendritic cells. Various pathogens can activate and modulate the function of dendritic cells. The presence of activated and mature dendritic cells in skin lesions of secondary syphilis has never been reported. In the present study, an immunohistochemical technique was used to determine the exact tissue distributions of CD83+ dendritic cells and interferon-gamma+ cells in skin lesions of patients with secondary syphilis. Immunohistochemical staining was performed by using formalin-fixed, paraffin-embedded sections. A small but significant subpopulation of CD83+ dendritic cells was found in the dermis. CD83+ dendritic cells were in close contact with lymphocytes. High-intensity staining of CD83 antigens was detected not only on the surface but also in the cytoplasm of dendritic cells. Infiltrating mononuclear cells were stained positively for CD4 or CD8, with CD8+ cells always being in the majority. A small number of interferon-gamma+ cells resembling mononuclear lymphoid cells were detected in all samples. These results provide in vivo support for the hypothesis that dendritic cells are activated by Treponema pallidum and that thus activated and mature CD83+ dendritic cells may play a role in the Th1 response in secondary syphilis.