We sought to identify genes affected by the aging process in the rat hippocampus using cDNA expression array analysis. RNA samples were extracted from the hippocampus of 2-month-old and 20-month-old rats and reverse-transcribed in the presence of [32P]dCTP. Membrane sets of Rat Atlas array 2 (Clontech) were hybridized with cDNA probe sets. Among a total of 1176 cDNAs, 23 showed significant (more than 2-fold) changes between groups. Eight genes were increased in the old group, while the remaining fifteen genes were decreased. Reverse transcription-polymerase chain reaction (RT-PCR) was used to validate the relative expression pattern obtained by the cDNA array. The results were consistent for 20 of the 23 genes tested. Most interesting findings were the decrease in expression of proteins for energy metabolism, proteins involved in secretion, and ribosomal proteins. The possible physiological significance of these changes are discussed.