Cholecystokinin, bombesin and pancreatic polypeptide are all reported to induce satiety in rodents. To test the hypothesis that cholecystokinin and bombesin induce satiety through release of pancreatic polypeptide, we compared the satiety inducing properties of each peptide in rats trained to eat a liquid diet (Magnacal). Studies were repeated after transabdominal truncal vagotomy (n = 8) or sham operation (n = 8). Peptides were given by intraperitoneal injection, and the volume of Magnacal ingested over a 2 hr period measured. After the injection of saline, unoperated rats (n = 16) ingested 30 +/- 2.3 ml of Magnacal. Caerulein (9 nmol/kg) and bombesin (27 nmol/kg) significantly inhibited food intake to 8 +/- 2.5 ml and 20 +/- 2.1 ml respectively. In contrast pancreatic polypeptide (27 nmol/kg) had no significant effect on food intake. Both caerulein and bombesin retained the ability to reduce food intake after vagotomy although the effects of caerulein were somewhat blunted. No significant changes in serum pancreatic poly peptide concentrations were observed after either the caerulein or bombesin injection. As both peptides release pancreatic polypeptide in higher mammals, species differences in release mechanisms appear to exist. We would conclude that caerulein and bombesin induced satiety is independent of pancreatic polypeptide release and that the weight loss induced by pancreatic polypeptide in obese rodents is unlikely to be due to induction of satiety.