Posttransplantation lymphoproliferative disorder (PTLD) is one of the most serious complications of solid-organ transplantation. It potentially is treatable in most cases, but current methods involve withdrawal or reduction of immunosuppression and the consequent risk for graft rejection. Sirolimus was shown in vivo and in vitro to limit proliferation of a number of malignant cell lines, including those of PTLD-derived cells. We present a case of disseminated PTLD in a patient with a renal transplant that resolved completely with conversion of immunosuppression to sirolimus. Graft function was maintained and improved with treatment. This offers a novel means of treating these patients and minimizing transplant loss.