Intact soleus and extensor digitorum longus muscles in the rat were freely grafted to the contralateral leg after either no preliminary tretment or 14 days prior denervation. Normal muscle grafts during the first week were characterized by a central zone of degenerating original muscle fibers (disappearing by 7–9 days) and a peripheral zone, containing regenerating muscle as well as small numbers of surviving original muscle fibers. A radial gradient of regeneration was established, with more mature muscle at the periphery and less mature muscle toward the center. Denervated grafts were characterized by rapid degeneration (within 2–3 days ) of original muscle fibers in the central area, rapid appearance of regenerating muscle fibers (e.g., cross striations by 5 days) with uniform levels of differentiation throughout the graft and larger numbers of surviving original muscle fibers at the periphery. During the first week, stages of muscle differentiation in denervated grafts were attained 1–2 days earlier than comparable stages in normal grafts. Later stages of muscle differentiation were similar in both types of grafts. Histochemical studies revealed a loss of enzyme activity (phosphorylase, ATPase and SDH) in the center of early (2–4-day) normal and denervated grafts. Denervated grafts, however, possessed a thicker peripheral rim of enzymatically active surviving muscle fibers than normal grafts. In both types of grafts the old muscle fibers in the center were replaced by enzymatically active regenerating muscle fibers which stained uniformly (ATPase) until 30 days. By 60 days a mixed fiber pattern had developed. Muscle spindles were found within the grafts.