The increased incidence of Kaposi's sarcoma (KS) in organ transplantation has been related to the KS herpesvirus and the permissive effect of immunosuppressive therapy. Calcineurin inhibitors are the cornerstone of immunosuppression in organ transplantation, although they could promote tumor progression. In contrast, sirolimus, a new immunosuppressive agent, exhibits potent antitumor activity. We postulated that conversion from cyclosporine to sirolimus in patients with KS could favor regression of KS lesions without increasing the risk of graft rejection. Two renal transplant recipients with KS underwent conversion from cyclosporine to sirolimus. Both patients showed complete regression of KS lesions and excellent clinical and functional results. Sirolimus offers a new and promising approach to the management of posttransplantation KS and probably to other types of malignancies in organ transplant recipients.