The effect of upper motor neuron regulation on skeletal muscle development was studied in the fetal pig. A region of the spinal cord at the level of the upper cervical vertebrae was destroyed by cauterization at 45 days of gestation in four pig fetuses. Five fetuses with intact spinal cords served as controls. Innervation and enzyme activities in the longissimus muscle, the ultrastructure and quantitation of satellite cells in the sartorius muscle, and plasma composition were evaluated at 110 days of gestation. The terminal innervation ratios were similar (P greater than 0.05) for muscles from control and cauterized fetuses. Endplate morphology was also similar. Therefore, innervation of newly formed primary fibers is not controlled by upper motor neurons after 45 days of gestation. Mean values for body weight, percentage of muscle dry weight, percentage of myofibers with myonuclei and plasma levels of protein, glucose, triglycerides, lactate, and creatine phosphokinase activity were similar (P greater than 0.05) between the two groups of fetuses. All but one muscle fiber examined was of the secondary fiber type. These observations suggest that the physiological maturity of the muscle was not appreciably altered even though glucose-6-phosphate dehydrogenase activity was higher (P greater than 0.05) and total phosphorylase activity was lower (P greater than 0.05) in the spinal cauterized fetuses than in the control group. The percentage of satellite cells was lower when based on the number of myofibers observed (P greater than 0.005) or on the number of nuclei contained within the basal lamina (P greater than 0.001) in the muscle of the spinal cauterized fetuses than in the control fetuses. The cytoplasm of satellite cells from the muscles of control fetuses was rich in organelles indicative of metabolic and mitotic activity whereas a paucity of such organelles was observed in the satellite cells of cauterized fetuses. Since the percentage of myofibers that had myonuclei was similar (P greater than 0.05) for the control and cauterized fetuses, it appeared that the myonuclear population was maintained by direct incorporation of the parent satellite cell.