The aim of this study was to determine if the exogenous administration of neurotrophic factors can rescue immature axotomized CNS neurons in vivo. After spinal cord hemisection in newborn rats, the exogenous administration of neurotrophic factors brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and nerve growth factor (NGF), prevents the retrograde cell death of axotomized red nucleus neurons (and other brain stem spinal neurons) in vivo. Rescue of red nucleus neurons was maintained in the presence of BDNF, but only transiently maintained by NT-3 and NGF. Neurons within the nucleus dorsalis (Clarke's nucleus) of the spinal cord are also axotomized by this lesion. The application of exogenous NT-3, but not NGF or BDNF, rescued Clarke's nucleus neurons. These observations indicate that neurotrophic factors play a crucial role in the survival of CNS neurons in vivo during development and after injury. Furthermore, these results indicate that particular populations of neurons are dependent upon specific neurotrophic support after injury.