Joint, muscle, and peripheral nerve allotransplantation was done with short-term cyclosporine immunosuppression. To investigate the effectiveness of this regimen, the allografts were examined after withdrawal of cyclosporine. Using inbred rats, vascularized orthotopic allotransplantation of the knee joint, rectus femoris muscle, and great saphenous nerve was done across a major histocompatibility complex barrier. Cyclosporine was administered for 4 to 6 weeks postoperatively, and the grafts were observed until Week 12. Long-term administration of cyclosporine and nonvascularized transplantation were used as controls. Although rejection of the allografts could be delayed for 2 to 3 weeks after the withdrawal of cyclosporine, all transplanted joints, muscles, and nerves eventually were rejected completely and immunotolerance could not be induced. The joint allografts at first achieved bony union, but eventually were destroyed because of pathologic fractures. In the group treated with long-term immunosuppression, the allografts showed no rejection and functional improvement was obtained. However, rats given a high dose (10 mg/kg per day) of cyclosporine died from adverse effects of the drug by Week 12. In the nonvascularized treatment group, the results were poor in every patient, and the need for graft vascularization for skeletal tissue allotransplantation was confirmed.