Generalized suppression of immunoglobulin G (IgG) synthesis detectable by depressed responses to heterologous antigens may be a mechanism by which certain parasites evade host defenses and establish chronic infections. To determine if such a mechanism occurs in syphilis, rabbits were infected with Treponema pallidum, and at weekly intervals thereafter these rabbits and uninfected controls were sensitized with SRBC. Seven days later the number of antibody-forming cells present in the spleen was determined by the Jerne plaque technique. After a transient suppression in the 1st week, IgM-PFC were elevated from up to 7 weeks after infection. The IgG response to SRBC was depressed early in infection and continued to decline to less than one-tenth of control levels over the next few weeks persisting throughout overt infection and returning to normal by the end of 2 months. IgG-PFC, and 2-ME-resistant hemagglutinins and hemolysins were also significantly depressed in infected rabbits after two immunizing doses of SRBC. These results suggest that the depressed IgG response caused by syphilitic infection may enable treponemes to evade host immunity by interfering with immunoregulatory mechanisms.