BACKGROUND: The role of angiogenesis in infectious processes is poorly studied. Some viruses have been linked to angiogenesis, but the role of bacteria and protozoa in inducing angiogenesis in chronic infections is poorly understood. OBJECTIVES: We examined the role of angiogenesis in syphilis, a common and often difficult-to-treat infectious disease, especially in the setting of HIV/AIDS. METHOD: Microvessel counts were performed on 27 paraffin-fixed sections of secondary syphilis by staining with monoclonal antibodies against CD31. In addition, immunohistochemistry was performed using antibodies against vascular endothelial growth factor (VEGF) to determine whether increased angiogenesis may be mediated, in part, through increased production of VEGF. RESULTS: The CD31 mean microvessel count in secondary syphilis sections was significantly higher than in normal control sections. VEGF intensity appeared increased in the patients with secondary syphilis. CONCLUSIONS: Infection with Treponema pallidum results in increased angiogenesis in secondary syphilis. The mechanism for increased angiogenesis may involve elaboration of angiogenic cytokines, such as VEGF and epidermal growth factor.