The purpose of the present study was to systematically investigate the effects of the mammalian neuropeptide Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2 (NPFF) on nociception, using the tail-flick test. We report that ICV administration of NPFF induces a rapid and short-lasting hyperesthesic effect during day or night, for doses ranging from 10 ng to 10 micrograms. During the night, this hyperesthesic effect is followed by a long-lasting analgesic effect, the magnitude of which is related to the magnitude of the hyperesthesic effect. In addition to this intrinsic effect of NPFF, we report that NPFF reverses morphine-induced analgesia and that the magnitude of the response elicited by NPFF increases as a function of morphine-induced analgesia.