T. pallidum penetrates intact mucous membranes or microscopic abrasions and, within hours, enters lymphatics and blood to produce systemic infection and metastatic foci. After a median incubation period of ~21 days (range, 2-6 weeks), the primary lesion (chancre) appears at the site of inoculation, persists for 4-6 weeks, and then heals spontaneously. Generalized parenchymal, constitutional, and mucocutaneous manifestations of secondary syphilis appear 6-8 weeks later despite high antibody titers, subsiding in 2-6 weeks. After a latent period, one-third of untreated pts eventually develop tertiary disease (syphilitic gummas, cardiovascular disease, neurologic disease).