To further confirm at the molecular level that neuronal apoptosis occurs in mesial temporal sclerosis (MTS), the main substrate of mesial temporal lobe epilepsy (MTLE), 24 resected sclerotic hippocampi from 24 patients with drug-resistant MTLE associated with MTS were studied microscopically, electronmicroscopically and immunohistochemically, with detection of expression of apoptosis-associated genes including bcl-2, p53, bax, fas and caspase-3. Early apoptosis changes were found morphologically in hippocampi from three patients with MTLE using transmission electron microscopy. Positive immunostained neurons for bcl-2, p53, fas and caspase-3 were found in the sclerotic hippocampi of 19/24, 14/24, 22/24 and 20/24 patients respectively, which was statistically different from controls. Correlative analysis showed the expression of p53, fas and caspase-3 were positively correlated with seizure frequency. Apoptosis may contribute to MTS, and seizures may induce apoptosis, and thus contribute to neuronal loss in MTS.