This study examines the level to which muscle regeneration proceeds in the absence of innervation. Regeneration was monitored in rat soleus muscles following localised injection of a snake toxin, notexin. Muscles which had been concomittantly denervated were compared with those that were normally innervated. Until 3-4 days following toxin administration regeneration is identical in both groups. The muscles contain new myotubes in place of the degenerated "parent" fibres. Thereafter, the non-denervated muscles grow rapidly and by 28 days their myofibres attain the size of those from the contralateral controls. Growth of denervated regenerating muscles, however, is retarded and is superseded by a gradual atrophy. In such muscles we further identify ultrastructural abnormalities from 7 days post-injection. These a re loss of individual myosin filaments and the presence of immature and abnormal configurations of the transverse system and triads. We, thus, conclude that innervation is an obligatory requirement for the restoration of normal myofibrillar and sarcotubular morphology, as well as growth, but is not necessary for the neo-formation of myofibres.