Inoculation of the causative agent of syphilis, Treponema pallidum into the testes of rabbits initiated the following sequence of events: 1) a rapid proliferation of organisms in the interstitial tissues of the testes, reaching a maximum at about 10-11 days after infection; 2) systemic spread of organisms primarily in the lymphoid organs; 3) a prompt immune response manifested by hyperplasia of T cell domains in draining lymph nodes and spleen, blast transformation responses of lymphoid cells to sonicates of T pallidum, the appearance of serum antibody, and the marked infiltration of the infected areas of the testes by T cells; 4) essential clearing of organisms identified by immunofluorescence from the infected site 10-14 days after infection associated with evolution of the inflammatory response from primarily a T cell infiltrate to a larger mononuclear cell type, and the immunofluorescent identification of presumptive T pallidum antigen in macrophages; 5) interstitial fibrosis or resolution 17-21 days after infection so that examination of infected testes from 1 to 24 months later reveals foci of tubular atrophy and fibrosis of varying size, alternating with regenerated tubules, separated by interstitial areas with only minimal fibrosis. During the long period of latency there is no evidence of atrophy or hypoplasia of the lymphoid organs and long-lasting T cell memory with regard to T pallidum sonicates is demonstrable. Reinfection of previously inoculated rabbits indicates partial protection at 25 days after infection followed by essentially complete protection after 55 days. It is concluded that there is a prompt and long-lasting immune response to T pallidum in experimentally infected rabbits. The main mechanism for destruction of infecting organisms appears to be T-cell-initiated macrophage-mediated destruction, but a role for antibody dependent phagocytosis cannot be ruled out. The reason that some organisms may survive in various body organs remains unknown, but possible explanations are presented.