Emesis was noted following intravenous bolus injections into dogs of a chromatographic subfraction derived from porcine small intestinal tissue extracts. The active agent was isolated from this subfraction using sequential ion-exchange and reverse-phase HPLC and demonstrated to be the recently identified regulatory peptide PYY. The threshold dose for PYY-induced emesis in the dog is less than 120 pmol/kg. Emesis was sometimes seen following large IV bolus doses of neuropeptide Y (NPY), but none was seen following IV injection of pancreatic polypeptide (PP). Dogs prepared with discrete, bilateral lesions of the area postrema were refractory to a suprathreshold emetic dose of PYY. PYY is the most potent, circulating emetic peptide identified to date.