While peripheral nerve reconstruction could benefit from the use of nerve allografts, long term immunosuppression for non-vital organ transplantation is controversial. This study investigated the effectiveness of short course Cyclosporin A immunosuppression. Fourteen Lewis (RTl1) rats were the recipients of 3 cm sciatic nerve grafts from ACI (RTla) donors, repaired to the transected sciatic nerve of the recipient animal. Animals were treated with Cyclosporin A (5 mg/kg/day) for eight weeks. Neuromuscular function was assessed every two weeks by sciatic function index determinations until 20 weeks. Electrophysiological, histological and morphological evaluations were performed at 14 (n = 6) and 20 weeks (n = 8) postengraftment. Rats had significantly improving functional studies from four to eight weeks (P = 0.01). Function decreased following cessation of Cyclosporin A treatment. Rats evaluated at 14 weeks had histological evidence of graft rejection with inflammatory cell infiltration, extensive demyelination and remyelination, and some Wallerian degeneration. Rats demonstrated improvement in morphological parameters and motor function from 14 to 20 weeks after engraftment. In this sciatic nerve allograft model, short course Cyclosporin A immunosuppression, although resulting in an initial episode of graft rejection, was successful in permitting good long term functional regeneration of neuromuscular function.