In order to better understand the mechanisms of alloimmunization occurring in transplantation, we studied the immune response of an inbred rat strain (WF) to varied presentation of alloantigens (LEW). Hyperimmunized rats acutely reject transplanted allografts and demonstrate direct cytotoxic activity, as well as an expanded potential to generate cytotoxic and suppressor cell activity. In contrast, passively and actively enhanced animals, which exhibit allograft tolerance, demonstrate endogenous suppressor cell activity and significantly reduced potential to generate cytotoxic and suppressor cell activity. Thus, the method of immunization of the same responder strain animals with identical alloantigens will determine whether rejection or tolerance is evidenced following transplantation. The suppressor T cell activity demonstrated in the enhanced animals appears to regulate the immune response by reducing cell proliferation when challenged with alloantigen. However, when restimulated in vitro with donor cells, splenic suppressor activity declines--i.e., there is not a secondary suppressor response.