Pseudoginsenoside-F11(PF11), an ocotillol type saponin isolated from Panax quinquefoliumL., has been shown to antagonize the behavioral actions of morphine. Biochemical experiments revealed that PF11could inhibit diprenorphine (DIP) binding with an IC50of ∼6.1 μM and reduced the binding potency of morphine in Chinese hamster ovary (CHO)-μ cells. Furthermore, PF11significantly attenuated morphine-stimulated 35SGTPγS binding in a dose dependent manner, and strongly decreased the efficacy of morphine to inhibit intracellular cAMP production. In addition, PF11pretreatment could also significantly inhibit naloxone induced cAMP overshoot in the morphine-pretreated cells. However, PF11per sehad no effect on either 35SGTPγS binding or intracellular cAMP accumulation. These data suggested that PF11antagonized the morphine stimulated opioid receptor signalling directly at the cellular level.