Semaphorin 3A (Sema3A) is a secreted repulsive axon guidance protein. It appears to play important roles in axon fasciculation, branching, neuronal migration, and tissue differentiation during embryonic development. In adults, Sema3A is expressed in spinal motoneurons and in some neurons in the brain. Here, we demonstrate changes in Sema3A expression in the spinal cord after complete transection and in the brain after spinal cord hemisection at the Th8 level in laboratory rats. Semi-quantitative reverse transcriptase-PCR analysis showed that the expression of Sema3A mRNA, which was present in the normal spinal cord, rapidly decreased after transection, reaching its lowest level 1 day after injury. Thereafter, Sema3A expression levels recovered and reached four-fifths of the normal level at 28 days. Double staining by in situ hybridization and fluorescence immunohistochemistry showed that Sema3A was expressed in NeuN-positive neurons, but not in glia in the spinal cord. Sema3A expression was up-regulated in the contralateral cerebral cortex and in the ipsilateral spinal trigeminal nucleus 1-3 days after spinal cord hemisection. It is likely that the up-regulation occurred in neurons whose descending fibers were transected. These results suggest that Sema3A is regulated differently in spinal motoneurons and brain neurons following axonal injury.