Patients with bone cancer report severe pain and receive μ-opioids. We developed a family of peptidomimetic δ-agonists, one of which H2N-Tyr-dVal-Gly-Phe-Ala-OH Symbol binds with a 1700× affinity at the δ versus μ receptor. To examine the systemic analgesic efficacy of this δ-agonist versus morphine in osteosarcoma pain, osteosarcoma cells are injected into one femur of the anesthetized mouse. After 10–18 days, a decalcification of the injected femur occurs along with a pronounced tactile allodynia. IP morphine and Symbol produced a dose-dependent reversal of allodynia with the respective ED50 values being 5.3 ± 1.9 mg/kg for morphine and 1.3 ± 0.3 mg/kg for [Symbol. Plotting peak effect versus area under the analgesic curve for doses of morphine and [Symbol revealed overlapping curves suggesting that for a given effect, [Symbol produced a similar duration of action as morphine. These effects were reversed by IP naloxone (3 mg/kg). IP naltrindole (1 mg/kg) preferentially reversed [Symbol. The upper dose effects of morphine but not [Symbol were limited by pronounced hyperactivity. No other effects were noted. These results show that IP [Symbol through a δ receptor produces analgesia equal in efficacy to that of morphine but with a 4.5-fold greater potency. Over the doses examined, morphine actions were side effect limited. The δ side effects were not so limited, suggesting a favorable therapeutic ratio for δ-agonists in this pain model. These studies suggest that a systemically delivered δ-opioid agonist has pronounced analgesic properties on a preclinical cancer pain model.