Disruption of the nerve supply results in the rapid loss of mass and contractile force in skeletal muscles. These losses are reversible to a high degree in short-term denervated muscles with grafting and nerve implantation. However, return is much poorer in long-term denervated muscles. This study examined the basis for the differences in the recovery of non-denervated and 7-month denervated rat extensor digitorum longus (EDL) muscles after grafting and nerve implantation. We found that the level of recovery is related to the ability of muscle fibers to degenerate and regenerate after grafting. Fibers within long-term denervated muscles do not degenerate and regenerate as well as those within muscles which are not denervated prior to grafting. The functional recovery of the denervated muscles is significantly improved when their fibers are induced to degenerate with the myotoxic anesthetic, Marcaine, Degeneration of these fibers is followed by massive regeneration. The finding that denervated muscles are capable of being restored to a significant level by inducing regeneration may be useful in the clinical treatment of denervated muscles.