Monovalent ligands were generated for oxymorphamine (M19) and MPEP (MG20). The mu opioid monovalent M19 dose-dependently reversed tactile hypersensitivity (black diamonds, ED50 value 1.1 nmol, 0.45–2.9). However, the MPEP based monovalent MG20 had no effect (white diamonds). When co-administered, MG20 had no effect on the potency of M19 (half-filled diamonds, ED50 value 0.9 nmol, 0.5–1.5). n = 7 mice per group.