THE number of neurotrophic factors found in the central nervous system is rapidly growing, but their functions in vivo are largely unknown. In the peripheral nervous system they promote the survival of developing and lesioned neurons and enhance nerve fibre growth and regeneration1-6. Here we study the effects of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) on the largest tract system leading from the brain to the spinal cord, the corticospinal tract (CST)7. The developing CST grows down the spinal cord during the first postnatal days and innervates its targets after a waiting period by collateral sprouting8-10. We find that NT-3 injected locally specifically enhances this sprouting, whereas BDNF has no effect. In adult rats, injection of NT-3 (but not BDNF) into the lesioned spinal cord increases the regenerative sprouting of the transected CST. The distance of growth of the sprouts is very restricted, but application of an antibody that neutralizes myelin-associated neurite growth inhibitory proteins" results in long-distance regeneration of CST fibres.