Several neurotrophic factors have been identified that influence neuronal populations during central nervous system development, maturation, and senescence. To examine the responsiveness of the intact and the lesioned adult mammalian spinal cord to neurotrophic factors, primary rat fibroblasts were genetically modified to produce and secrete human nerve growth factor (NGF). These NGF-producing cells were then grafted to nonlesioned or lesioned adult rat spinal cords for periods of up to 1 year in vivo. Robust outgrowth of sensory and noradrenergic neurites was elicited by grafts in the previously nonlesioned spinal cord. Equally robust growth of sensory and noradrenergic neurites was observed in the lesioned spinal cord; in addition, partial sprouting of local motor neurites was elicited in the lesioned spinal cord. Thus, multiple neuritic populations of the adult spinal cord respond to neurotrophic factors by extending neurites, and this responsiveness is maintained and extended after major injury. Nerve growth factor delivered by somatic gene transfer may be a useful means of promoting axon regrowth in the injured spinal cord.