Neuropeptide Y (NPY), peptide YY (PYY), and pancreatic polypeptide (PP) are endogenous 36-amino acid peptides belonging to the same family. Different receptor subtypes have been identified in the NPY/PYY/PP family (1), and mammalian subtypes are now classified collectively as NPY receptors, several of which (namely Y1, Y2, Y4, Y5, and Y6) have been cloned (2–10). Based on studies using full-length peptides, C- or N-terminal fragments, and modified peptides of the NPY/PYY/PP family (11,12), the NPY Y5 receptor subtype was proposed as a mediator of NPY-induced feeding. At the time when the NPY Y5 receptor was cloned, neither NPY Y5 antagonists nor NPY Y5 knockout mice were available. Therefore we used an antisense oligodeoxynucleotide (antisense ODN) strategy to assess the proposed role of the NPY Y5 receptor subtype in the regulation of feeding.