Fetal spinal cord cells, Schwann cells and neurotrophins all have the capacity to promote repair of injured spinal cord in animal models. To explore the possibility of using these approaches to treat clinical patients, we have examined whether a combination of these protocols produces functional and anatomical improvement. The spinal cords of adult rats (n=16) were injured with a modified New York University (NYU) device (10 gram.5cm). One week after injury, the injured cords were injected with Dulbecco-modified Eagles Medium (DMEM, control group), or fetal spinal cord cell suspension (FSCS) plus nerve growth factor (NGF) gene-modified Schwann cells (SC) and brain-derived neurotrophic factor (BDNF) gene-modified SC (treatment group). The rats were subjected to BBB (Basso, Beattie, Bresnahan, Exp. Neurol. 139:244, 1996) behavioral tests. Anterograde tracing of corticospinal tract was performed before sacrifice 3 months after the treatment. The results showed that the combination treatment elicited a robust growth of corticospinal axons within and beyond the injury site. A dramatic functional recovery in the treatment group was observed compared with the control group. We conclude that the combination of FSCS with genetically modified Schwann cells over-expressing NGF and BDNF was an effective protocol for the treatment of severe spinal cord injury.