SUMMARY In the absence of earlier reported success in the free grafting of autogenous skeletal muscle to orthotopic sites, the present investigation varied the grafting procedure in two ways. First, only complete muscle bellies were transplanted so that the full length of all constituent muscle fibres were included in the graft. Secondly, each complete muscle entity was denervated 14-21 days before transplantation so that the resultant enzyme changes might alter the muscle metaboism to a more economic level of aerobic type (increasing vascularity). By this change, the transplant might better survive the initial period of ischaemia and become more effectively vascularized by direct anastomosis of graft and host vessels at the recipient site. In 8 dogs, when 20 free autogenous grafts of skeletal muscle were applied as orthotopic transplants which included the complete muscle belly, microscopic survival occurred in half the grafts but never to more than 5-10% of the original volume of the graft. In 4 dogs, when 8 similar grafts were transplanted 2-3 weeks after preliminary denervation, 6 survived in up to 80% of the original gross volume of the grafts, with histologically normal muscle constituting as much as three-quarters of the surviving graft. A source of innervation limited to one extremity of the graft allowed axonal proliferation to produce reinnervation over a distance of 5 cm of grafted muscle in 6 months. The reinnervation of muscle grafts was confirmed by histological and histochemical investigation, as well as direct electrical stimulation. In a single human patient suffering from facial paralysis, a free graft of the extensor digitorum brevis muscle of the foot was transplanted to the face, 2 weeks after denervation, to reanimate the paralyzed eyelids, with clinically complete success confirmed by electromyography. Histologically normal muscle, the presence of innervating axons, and reinnervated motor end plates were demonstrated in the grafts 8 months after transplantation.