Beta-Endorphin immunoreactivity has been localized in 12 regions of the post mortem human cerebral cortex by using a polyclonal antiserum specifically recognizing the peptide. Cell bodies and proximal dendrites of certain cortical neurons (mostly interneurons) were densely populated with nerve endings immunoreactive for beta-endorphin. These 'endorphinoceptive' nerve cells were most abundantly present in the cingulate cortex as well as in the Gyri frontales superior and medius. In other cortical areas they appeared with much lower frequency (Gyri ambiens, semilunaris, parahippocampalis, temporalis). Our data show that the human cerebral cortex receives an endorphinergic innervation which might be of potential interest with regard to certain neuropsychiatric and neurodegenerative disorders.