Following postcommissural fornix transection we have investigated the postaxotomy transcriptional program in the subiculum where the injured axons originate. cDNA array hybridization revealed 125 genes that were specifically regulated as the injured neurons passed through three distinct postlesion (PL) stages comprising (i). early phase of injury and axon degeneration, (ii). sprouting phase of the proximal stump, and (iii). axonal growth arrest at the lesion scar. Numerous genes were detected which have, so far, not been associated with axotomy or axonal growth. Following the early lesion response that is characterized predominantly by down-regulation of genes at 1 day PL, neurons switch to a sprouting program with the majority of genes up-regulated at 7 days PL. However, the latter program of gene expression is not maintained but largely reversed (at 3 weeks PL) to the initial profile as axonal growth is blocked at the lesion barrier, indicating retrograde signaling that leads to down-regulation of neuronal genes previously up-regulated during axon sprouting.