Spinal cord injury (SCI) often results in necrotic changes leading to cavity formation and glial scar tissue in the lesion zone. We have examined the effects of continuous topical administration of brain-derived neurotrophic factor (BDNF) on cavity formation and neuronal death after SCI. Following retrograde prelabeling of the tibial motoneurons in the L4-L6 spinal cord segments with the fluorescent dye Fast blue, a spinal hemisection was performed in the L5 segment. At 4 weeks postoperatively, only 66% of the labeled motoneurons remained in the untreated animals, while BDNF treatment resulted in a significant reduction in size of the lesion cavity and 92% motoneuron survival. A therapeutic potential of BDNF in the early treatment of SCI is suggested.