F3/Contactin (F3), a neural adhesion molecule, is known to be involved in developmental and regenerative processes in the brain. We have investigated age-related change in the expression of F3 mRNA and protein in the Wistar rat brain using immunohistochemistry and in situ hybridization. From 3 months to 24 months, no obvious change in the amount of F3 protein was observed in cerebral cortex, hippocampus and cerebellum. However, in 30-month-old rats a significant decrease in F3 protein was found in the hippocampus. A specific decrease of density of F3 immunostaining and F3 mRNA expression was observed in the pyramidal neurons of CA1 and the granule cells in dentate gyrus. The specific decrease of F3 in the hippocampus at late stage of aging may be related to memory deficient in old age.