Opioid receptor binding was evaluated in parahippocampal cortex (PHC) obtained from patients with intractable mesial temporal lobe epilepsy (MTLE) with and without subacute high frequency electrical stimulation (HFS) in this brain area. Mu, delta and nociceptin receptor binding was determined by autoradiography in PHC of five patients (ESAE group) with MTLE history of 14.8±2.5 years and seizure frequency of 11±2.9 per month, two of them (40%) with mesial sclerosis. This group demonstrated antiepileptic effects following subacute HFS (130Hz, 450μs, 200–400μA), applied continuously during 16–20 days in PHC. Values were compared with those obtained from patients with severe MTLE (history of 21.7±2.8 years and seizure frequency of 28.2±14 per month) in whom electrical stimulation did not induce antiepileptic effects (ESWAE group, n=4), patients with MTLE in whom no electrical stimulation was applied (MTLE group, n=4) and autopsy material acquired from subjects without epilepsy (n=4 obtained from three subjects). Enhanced 3H-DAMGO (MTLE, 755%; ESAE, 375%; ESWAE, 693%), 3H-DPDPE (MTLE, 242%; ESAE, 80%; ESWAE, 346%) and 3H-nociceptin (MTLE, 424%; ESAE, 217%; ESWAE, 451%) binding was detected in the PHC of all epileptic groups. However, tissue obtained from ESAE group demonstrated lower opioid receptor binding (3H-DAMGO, 44.5%, p<0.05; 3H-DPDPE, 47%, p<0.05; 3H-nociceptin, 39.3%, p<0.5) when compared with MTLE group. The present results indicate that a high effectiveness to the antiepileptic effects induced by HFS is associated with reduced opioid peptide binding.