In the spleen of mice immunized with bromelin treated rat red blood cells (RBC), the number of PFC against bromelin treated isologous RBC increased, although immunization with non-treated rat RBC or bromelin treated isologous RBC gave no increase in number of these PFC. This immune response was found to be T-independent and the PFC developed are exclusively of direct or Ig-M type. In the secondary immune response, production of these PFC was depressed rather than increased. This can be thought of as one of the defence mechanisms against overproduction of autoantibodies in confrontation to foreign antigens cross-reactive with self antigenic determinants. This depressed secondary immune response can be adoptively transferred by primed spleen cells but no active suppressor effect was found. We concluded that clonal elimination by exhaustive differentiation may be operative in this depressed secondary immune response.