BACKGROUND: On the basis of positive results in studies of the transplantation of pig extremities and the information exchanged at an international symposium on composite tissue transplantation, we developed a protocol for human hand transplantation. METHODS: After a comprehensive pretransplantation evaluation and informed-consent process, the left hand of a 58-year-old cadaveric donor, matched for size, sex, and skin tone, was transplanted to a 37-year-old man who had lost his dominant left hand 13 years earlier. Immunosuppression consisted of basiliximab for induction therapy and tacrolimus, mycophenolate mofetil, and prednisone for maintenance therapy. RESULTS: The cold-ischemia time of the donor hand was 310 minutes. There were no intraoperative or early postoperative complications. Moderate acute cellular rejection of the skin of the graft developed 6, 20, and 27 weeks after transplantation. All three episodes resolved completely after treatment with intravenous methylprednisolone and topical tacrolimus and clobetasol. Temperature, pain, and pressure sensation had developed in the hand and fingers by one year. At one year, the patient had regained the ability to perform many functional activities with his left hand that he had not been able to perform with his prosthesis, such as throwing a baseball, turning the pages of a newspaper, writing, and tying his shoelaces. CONCLUSIONS: Early success has been achieved in hand transplantation with the use of currently available immunosuppressive drugs.