Trauma to the central nervous system (CNS) and peripheral nervous system (PNS) cause an inflammatory response that is dichotomous and may support or inhibit subsequent regenerative capacity. However, very little is known about the patterns of gene expression in the injured tissues, nuclei, or ganglia. We have used complementary DNA microarrays to monitor gene expression in models of peripheral nerve regeneration and spinal cord trauma and in peripheral and central glia. The expression profile of the regenerating dorsal root ganglion (DRG) showed a number of gene groups whose function is consistent with metabolic activation and neurite elongation. The absence of cell cycle–related gene activation and tissue mitosis in the DRG suggests the existence of a modified form of the cell cycle, the "regeneration cycle." In addition, a cluster of 111 genes up-regulated in the DRG were identical to genes down-regulated in activated Schwann cells (and a subset of oligodendrocytes), indicating that components of the gene-expression program are highly conserved and can be reciprocally regulated. The gene expression profile in the injured spinal cord following methylprednisolone treatment is consistent with the reduction in messenger RNA and protein synthesis levels and the provision of neuroprotection through the up-regulation of genes encoding antioxidants, growth factors, and matrix proteins. Gene-expression monitoring is useful in characterization of the genetic response following PNS or CNS trauma and for the identification of leads for the development of novel therapeutic targets.