Necrosis and widespread central nucleation of skeletal muscle cells, which are the main features of skeletal muscle pathology in genetically dystrophic hamsters (UMX-7.1 strain), were not present in muscles of 45- to 65-day-old animals which had been surgically denervated at 15 to 18 days of age. Necrosis and widespread central nucleation were also absent in hind leg muscles at 30 to 60 days of age after transection of the high thoracic spinal cord at 15 to 18 days. Normal excitation or contraction of the skeletal muscle fibers in early age appears necessary for the microscopic pathological expression of the dystrophic gene in skeletal muscles in the UMX-7.1 strain hamsters. These experiments constitute a rare and clear example of consistent prevention of skeletal muscle cell destruction in vivo in an inherited myopathy.