The effect of neuropeptide FF (NPFF), a mammalian FMRFamide-like peptide with antiopioid activity, on food intake was investigated in food-deprived rat. The ICV administration of NPFF (5 or 10 micrograms/rat) reduced food intake during the first 60 min after administration. ICV injection of naloxone (10 or 100 micrograms/rat), an opioid antagonist, also decreased food intake. However, the combination of NPFF and naloxone showed no additivity in the anorexigenic effect, suggesting that NPFF and naloxone reduced food intake by the common mechanism. These results indicate that NPFF may function as an endogenous anorexigenic peptide with anitiopioid function.