Identification of genes that are specifically expressed in the hippocampus of senescence accelerated mouse (SAM) is important for understanding the molecular basis of the pathological changes in the brain and of the deterioration of learning and memory in SAM-prone/8 (SAMP8), a substrain of SAM. The differential display technique was applied to compare mRNAs expression between SAMP8 and SAM-resistance 1 (SAMR1), another substrain of SAM. Complementary DNA fragments corresponding to several apparently differentially expressed mRNAs were recovered and sequenced. Six differentially expressed cDNA bands were identified. Sequence analyses demonstrated that W4 and W5 cDNA fragments corresponded to unknown genes. W1 and W6 showed 66.1 and 62.3% homology to rat GTP-exchange protein (eIF-2B) and rat phospholipase D, respectively, while W2 and W3 showed 89.2 and 90.8% homology to human bullous pemphigoid antigen and human glucogen debranching enzyme isoform 1/2/3/4/6, respectively. The results suggested that these genes are closely related to the malfunction of the brain in SAM.