Objective: To investigate the expression of PSD-93 mRNA and NR2B mRNA in the brain tissue from the patients with epilepsy so as to explore the possible mechanisms of the pathogenesis of the epilepsy. Methods: Fifty-six patients with epilepsy were divided into intractable epilepsy (IE) and non-intractable epilepsy (NIE) groups. cDNA microarrays prepared from the brain tissues obtained from these two groups were scanned and comparison to those from the non-epileptogenic control (C) was made. Expression level of PSD-93mRNA and NR2BmRNA were examined by reverse transcription polymerase chain reaction (GAPDH gene, internal control). Expression ratio (target gene/GAPDH) was used to evaluate each gene relative expression level. Results: The cDNA microarray analysis showed that the expression of PSD-93 mRNA related to the function of NMDAR-NO signal transduction pathway was significantly higher in epilepsy patients than those in the controlled group. The results of RT-PCR were consistent with those of the cDNA microarrays. The relative expression ratio of PSD-93 in patients with non-epileptogenic control, NIE, and IE was 0.159, 0.368, and 0.341, respectively. Correspondingly, that of NR2B was 0.198, 0.738, and 0.903, respectively. The expressions of PSD-93 and NR2B in the NIE and IE were significantly higher than those of control, respectively (P < 0.05). However, there was no significantly difference the expression of PSD-93 between NIE and IE. (P > 0.05), neither do that of NR2B (P > 0.05). Conclusions: The upregulated expressions of PSD-93 mRNA and NR2BmRNA may be involved in the pathogenesis of epilepsy. (C) 2007 Elsevier Inc. All rights reserved.