Transplant patients are at particular risk for developing post-transplant lymphoproliferative disease (PTLD) following administration of immunosuppressive therapy. In many cases the PTLD lesions express Epstein-Barr virus (EBV) latent and lytic genes as well as elevated levels of host cytokines. An outline of the potential contributions of EBV, host cytokines and T cells, and the immunosuppressive cyclosporine A, tacrolimus, and anti-CD3 antibody in the mechanism and pathogenesis of this disease is presented and discussed.