The synthetic decapeptide Ser-Leu-Thr-Cys-Leu-Val-Lys-Gly-Phe-Tyr (termed immunorphin) corresponding to the sequence 364-373 of the CH3 domain of human immunoglobulin G heavy chain and its synthetic fragment VKGFY were found to compete with 125I-labeled β-endorphin for high-affinity naloxone-insensitive binding sites on membranes isolated from the rat brain cortex (Ki=1.18±0.09 and 1.58±0.11nM, respectively). The binding specificity study revealed that these binding sites were insensitive not only to naloxone but to [Met5]enkephalin and [Leu5]enkephalin as well. The Kd values characterizing the specific binding of 125I-labeled immunorphin and its fragment Val-Lys-Gly-Phe-Tyr to these binding sites were determined to be 2.93±0.27nM and 3.17±0.29nM, respectively. © 2002 Elsevier Science Inc. All rights reserved.