Transplantation tolerance was the phenomenon that first directed the attention of immunologists and experimental biologists to the idea of an induced specific immunological nonreactivity. This was so for two reasons:(i) it provided an almost exact experimental model of the process envisaged by Burnet & Fenner (1949) as that which would make it possible for an organism to distinguish between self and non-self substances, and (ii) it gave the first assurance that the barrier which normally prohibits the transplantation of tissues between nrn'mais of different genetic make-up could be surmounted. Whether transplantation tolerance is a central failure of the immune response (as Billingham, Brent & Medawar (1956) originally supposed), or is due to some peripheral interference with the inception or execution of the immune response, is a subject of current debate. There has been a tendency in recent publications to link the" central failure" interpretation to the hypothesis that tolerance is the outcome of an elimination of a clone of specifically immunecompetent cells. Although this is methodologically inexact, the great strength of the clonal theory is that it accounts for both immunity and tolerance. At all events, it is a defining characteristic of the central failure theory that, in a fully tolerant animal, cells capable of reacting upon the tolerance-conferring antigen should not be present. In all current forms of the peripheral theory, by contrast, it is assumed that hostile cells are present but are prevented by one means or another from attacking their targets. Perhaps the important distinction is between tolerance as essential non-reactivity and tolerance as the consequence of an active suppression of the immune response. Both mechanisms will be discussed.