Synaptic vesicle protein 2A (SV2A) involvement has been reported in the animal models of epilepsy. The aim of this study was to investigate the expression of SV2A in human intractable epilepsy (IE) brain tissue. Using immunohistochemistry, immunofluorescence, and Western blot, we detected SV2A expression in tissue samples from the anterior temporal neocortex of 33 patients who had been surgically treated for IE. We compared these tissues with nine histologically normal anterior temporal lobe samples from controls. SV2A immunoreactive staining was 0.1651+/-0.0564 in patient group and 0.2347+/-0.0187 in the control group (p<0.05) using immunohistochemistry, and this finding was consistently observed with Western blot analysis (0.1727 +/- 0.0471 versus 0.3976+/-0.0983, p<0.05). Immunofluorescence staining showed that SV2A was mainly accumulated in neurons. Our findings demonstrate that down-regulation of SV2A is present in patients with temporal lobe epilepsy.