The clinical course and outcome of 5 adult patients who underwent orthotopic liver transplantation (OLT) and developed Kaposi's sarcoma (KS) is reported. From October 1986 to July 2000, a total of 459 patients underwent 499 OLTs at our hospital. The immunosuppressive regimen consisted of cyclosporine, azathioprine, prednisone, and antithymocyte globulin. Tacrolimus was administered only in selected patients. Five patients developed KS, and the pathological diagnosis was established months 9 to 23 after OLT. Four of 5 patients died of KS, surviving 0 to 6 months after pathological diagnosis. The fifth patient, with KS confined to the skin, is disease free 6 months after diagnosis. All patients were treated with reduction of immunosuppressive therapy and/or chemotherapy. Retrospective molecular investigation by polymerase chain reaction for human herpesvirus type 8 DNA detected specific viral sequences in histological specimens of tissues involved by KS. In our experience with adult liver transplant recipients, we registered a slightly lower prevalence of KS compared with other reported data, but observed a high rate of graft involvement and mortality.