Despite major advances resulting from the development of new immunosuppressive drugs in recent years, the field of clinical transplantation is currently limited by inadequate organ availability, chronic rejection, and complications of chronic, nonspecific immunosuppressive therapy. Because of the organ shortage, extensive research has recently focused on the potential to use donors from other species, i.e., xenotransplantation. The best way to avoid the problems of chronic rejection and complications of immunosuppressive therapy, and to overcome the considerable immunologic barriers to xenotransplantation, would be to induce a state of systemic tolerance to the donor in the recipient. Recent developments in the understanding of mechanisms of central and peripheral T cell toler‐ance have led to new strategies for inducing tolerance in experimental models, some of which are already being evaluated clinically.—Sykes, M. Immunobiology of transplantation. FASEB J. 10, 721–730 (1996)