Bivalent ligands containing the oxymorphamine or naltrexamine pharmacophores connected to spacers of varying length were synthesized and evaluated for their selectivity at μ, K, and δ opioid receptors. The oxymorphamine bivalent ligands (1–8) behaved as μ agonists on the electrically stimulated guinea pig ileum longitudinal muscle preparation (GPI). The spacer that conferred peak agonist activity in these series contains a total of four glycyl units (n = 2). Binding studies with guinea pig brain membranes showed a qualitatively similar profile at μ receptors as a function of spacer length. Also, δ receptor selectivity increased as the spacer was lengthened. The naltrexamine bivalent ligands (9–13) effectively antagonized the μ receptor agonist morphine in the GPI at the same optimal spacer length (n = 2) as in the agonist series. However, the peak antagonism of ethylketazocine, a k receptor agonist, occurred with the bivalent ligand 9 containing the shortest spacer (n = 0), and it was found that 9 is the most selective k antagonist in the series. While receptor binding roughly parallels that of k antagonist activity in the GPI, no correlation between binding and antagonist activity was observed at μ opioid receptors. The possible significance of these results is discussed.