Successful induction of bone marrow chimerism is the most potent means of inducing specific transplantation tolerance across major histocompatibility barriers. Reliable, non-toxic methods of achieving such chimerism could obviate the need for chronic immunosuppressive therapy in clinical organ transplantation. Some novel conditioning protocols have recently been developed which permit the achievement of this goal in animal models. Recent developments have led to a greater understanding of the mechanisms leading to the induction of tolerance in each of these models.