PURPOSE The main goal of the present study was to evaluate possible alterations in opioid peptide and muscarinic receptors in human neocortical epileptic focus and the surrounding area removed from patients with pharmacologically resistant epilepsy and epilepsy secondary to cerebral lesion by tumor or other causes. METHODS In vitro quantitative autoradiography experiments were carried out to label mu, delta, and muscarinic receptors of neocortical epileptic focus and surrounding area obtained from patients with pharmacologically resistant primary epilepsy and epilepsy caused by tumors and angioma cavernosa, and compared with neocortex obtained from patients with dementia and tumors without epilepsy. RESULTS The mu receptor levels were lower in surrounding areas (-46%). The delta receptor binding was reduced in epileptic focus obtained from patients with epilepsy secondary to cerebral lesion (-25%) and surrounding areas (-31%). In contrast, muscarinic receptor levels were higher in the focus from patients with primary epilepsy (layers I-II, 52%; layers III-IV, 44%; layers V-VI, 36%). CONCLUSIONS It is suggested that the increased muscarinic receptors in the epileptic focus and the decreased mu and delta receptors in the surrounding area are associated with the initiation and propagation of seizure activity in human epileptogenic neocortex.