Advances in immunotoxin formulation have enabled application of this reagent to tolerance induction in primate preclinical models. The most successful paradigm transiently ablates recipient T cells, enabling engraftment into an immunologically permissive environment. The greatest success in stable tolerance induction (without chronic rejection) has been with the combination of immunotoxin and 15-deoxyspergualin. 15-deoxyspergualin complements immunotoxin by reducing cytokine production and blocking dendritic cell maturation and antigen presentation. Thus, we have been able to establish durable, long-term immunologic T- and B-cell tolerance (without donor-specific alloimmunity) to MHC-mismatched macaque allografts, satisfying the most stringent criteria for true toilerance.