To identify genes that render the adult-injured spinal cord nonpermissive and the embryonic spinal cord permissive to regeneration, we used subtraction hybridization and suppression PCR to generate subtractive cDNA populations representing (1) genes expressed in the embryonic but not in the adult-injured or uninjured spinal cords, (2) genes expressed in the adult-injured but not in the embryonic or adult-uninjured spinal cords, and (3) genes expressed in the embryonic and adult-injured spinal cords but not in the adult-uninjured spinal cord. Between 85 and 98% of the cDNAs identified are differentially represented in each population. Genes in each cDNA population were identified by microarray hybridization. Genes involved in inflammation, apoptosis, and neuroprotection were overrepresented in injured spinal cord cDNA, whereas genes involved in cell signaling and differentiation were overrepresented in the embryonic cDNA. This gene expression profiling suggests new hypotheses regarding the genes involved in inhibition and promotion of spinal cord regeneration.