Allogeneic grafts have many advantages over autogenous grafts. An experimental rat model using the great saphenous nerve was developed to study the reconstruction of long peripheral nerve defects with vascularized allogeneic nerve grafts, and the effects of cyclosporine therapy on graft survival were assessed. In animals receiving short-term immunosuppression, the number of regenerated axons increased steadily during the treatment, but rejection began immediately after cyclosporine was discontinued. As the tissues transplanted with the nerves underwent necrosis, the grafts showed demyelination. In contrast, in animals receiving long-term cyclosporine therapy, nerve regeneration assessed in terms of the myelinated axon count was excellent until at least 12 weeks postoperatively but was less active than in vascularized autografts or conventional allografts. These results indicate that the short-term immunosuppressive therapy with cyclosporine cannot produce immunological tolerance of vascularized nerve allografts. In addition, even when administration of cyclosporine was prolonged, nerve regeneration did not exceed that in autografts.