Neuropeptide FF (NPFF) is an endogenous peptide able to modulate opioid functions via specific receptors localized in spinal cord and brain that could be involved in the establishment of opioid tolerance. NPFF attenuated opioid analgesia in rats and mice. During ontogeny in mice the NPFF analogue (1DME)Y8Famide (1) did modulate morphine analgesia depending on the dose and on the test. A low dose inhibited morphine analgesia in the tail immersion test whereas a higher dose increased this effect. in adult mice, only the inhibition of morphine analgesia by (1DME)Y8Famide was observed. NPFF effects could be due to a rise in intracellular Ca2+ as measured in the superficial layers of the dorsal horn in slices of mouse spinal cord.