A number of receptors for the pancreatic polypeptide-fold peptides are proposed based on findings from pharmacology and molecular biology studies. Neuropeptide Y and peptide YY have similar affinity for neuropeptide Y Y 1 and neuropeptide Y Y 2 while pancreatic polypeptide has highest affinity for pancreatic polypeptide 1. Pro 3 4 -substituted analogs of neuropeptide Y and peptide YY have selectivity for neuropeptide Y Y 1 over neuropeptide Y Y 2 receptors. In the present study, we found that one such neuropeptide Y Y 1 -selective radioligand, [ 1 2 5 I][Leu 3 1 ,Pro 3 4 ]peptide YY, also binds with high affinity to the pancreatic polypeptide 1 receptor. Therefore, caution needs to be exercised when using Pro 3 4 -analogs to define the neuropeptide Y Y 1 receptor in vivo and using tissue preparations.