In an effort to develop selective antagonists for κ opioid receptors, bivalent ligands that contain opioid antagonist pharmacophores derived from naltrexone or other morphinans were synthesized and tested on the guinea pig ileum (GPI) and mouse vas deferens (MVD) preparations. The minimum requirements for κ selectivity are at least one free phenolic OH group and one N-cyclopropyl or N-allyl substituent. Several compounds (3, 8,10) with κ selectivity as good as or better than norbinaltorphimine (nor-BNI, 2) were discovered. The structure-activity relationship revealed that the pyrrole ring functions strictly as a spacer and does not contribute to κ selectivity. The pharmacologic data suggest that only one antagonist pharmacophore may be required for κ selectivity and that the other morphinan portion of the molecule confers selectivity by interacting with a unique subsite proximal to the antagonist pharmacophore recognition locus.