Removal of retinal input from a restricted region of adult cat visual cortex leads to a substantial reorganization of the retinotopy within the sensory-deprived cortical zone. Little is known about the molecular mechanisms underlying this reorganization. We used differential mRNA display (DDRT-PCR) to compare gene expression patterns between normal control and reorganizing visual cortex (area 17–18), 3 days after induction of central retinal lesions. Systematic screening revealed a decrease in the mRNA encoding cyclophilin A in lesion-affected cortex. In situ hybridization and competitive PCR confirmed the decreased cyclophilin A mRNA levels in reorganizing cortex and extended this finding to longer postlesion survival times as well. Western blotting and immunocytochemistry extended these data to the protein level. In situ hybridization and immunocytochemistry further demonstrated that cyclophilin A mRNA and protein are present in neurons. To exclude the possibility that differences in neuronal activity per se can induce alterations in cyclophilin A mRNA and protein expression, we analyzed cyclophilin A expression in the dorsal lateral geniculate nucleus (dLGN) of retinally lesioned cats and in area 17 and the dLGN of isolated hemisphere cats. In these control experiments cyclophilin A mRNA and protein were distributed as in normal control subjects indicating that the decreased cyclophilin A levels, as observed in sensory-deprived area 17 of retinal lesion cats, are not merely a reflection of changes in neuronal activity. Instead our findings identify cyclophilin A, classically considered a housekeeping gene, as a gene with a brain plasticity-related expression in the central nervous system.