Neuropeptide Y (NPY), peptide YY (PYY), and pancreatic polypeptide (PP) are regulatory peptides that constitute a new family of gastrointestinal and neural peptides. The influence of vagal integrity on NPY, PYY, and PP basal and postprandial release was evaluated using a new technique of reversible cryogenic cervical vagal blockade in an awake canine model. Cooling coils were placed around bilateral cervical vagal trunks in five dogs along with omocervical arterial catheters. Vagal transmission was monitored by pulse and arterial pressure monitoring. Cryogenic blockade of vagal nerves was performed by circulating a mixture of 0 degrees C ethanol and water through the cooling coils. NPY, PYY, and PP were measured using standard radioimmunoassays. Vagal cooling decreased basal NPY and PYY levels (P less than 0.05) but not PP. After a standard meal, vagal cooling blocked the postprandial rise seen in circulating NPY and PP (P less than 0.05). These data demonstrate a technique of reversible vagal blockade to evaluate the role of cervical vagal integrity in gastrointestinal endocrinology. Cryogenic vagal blockade inhibits the postprandial rise of circulating PP into the circulation. Vagal pathways appear to contribute to fasting activity of PYY and NPY releasing cells. Inhibited meal-stimulated release of NPY supports a role for vagal modulation of postprandial NPY release into the circulation.