Spleens from 1-20-wk-old guinea pigs infectedin uterowithTreponema pallidumand age-matched controls, born to normal and heat-killed (56°C, 2 h.)T. pallidum-injected mothers, were examined for theirin vitrolymphoproliferative response to phytohemagglutinin, concanavalin A, and lipopolysaccharide. Additionally. T cell surface markers (μ-chain, pan T, CD4, and CD8) were determined in spleen, lymph node, and peripheral blood from 10-wk infected and normal pups by single and dual parameter fluorescence-activated cell sorter analysis. Compared with control animals, congenitally infected animals showed a remarkable prolonged naive-type of immune response as reflected by the higher(p< 0.01) proliferative responses to both T cell mitogens (up to 20 wk of age), and the weaker response to the B cell mitogen, significantly different (p< 0.01) at 10 wk of age. As opposed to controls, in all organs examined the level of CD8+(cytotoxic/suppressor) T cells was significantly diminished (p< 0.01); consequently, the CD4/CD8 ratio was significantly elevated (p< 0.05). The role of C4 complement component and the nature and potential role of the immature T and B lymphocyte responses in asymptomatic congenital syphilis is discussed.