The blastogenic response of nylon wool-separated peripheral-blood lymphocytes from Treponema pallidum-infected rabbits was tested in vitro with mitogens and T. pallidum antigens. The mitogenic response of the enriched T-cell population to concanavalin A and phytohemagglutinin was depressed during the first 3 to 4 weeks of infection, similar to the pattern observed with unfractionated cells. Shortly thereafter, levels of blastogenesis returned to values of uninfected cultures. Enhanced blast transformation was seen immediately when purified T-cells from infected rabbits were exposed in vitro to T. pallidum antigens. Although these relatively high levels of blastogenesis were maintained for the duration of the experiment, cultures of unfractionated lymphocytes from infected rabbits did not exhibit an increased blastogenic response to the same antigen preparation until 3 to 4 weeks after infection. Autologous serum from infected rabbits decreased the lymphocyte response to T. pallidum antigen. The stimulatory effects of anti-immunoglobulin G and lipopolysaccharide on nylon wool-fractionated or unfractionated lymphocytes from both infected and control rabbits were similar throughout the course of infection. During the first 6 weeks of experimental disease, there was a 25 to 31% increase in the number of lymphocytes circulating in the peripheral blood of T. pallidum-infected rabbits.