Pancreatic polypeptide (PP) may function as a regulator of satiety. Its secretion is impaired in certain animal models of obesity and the administration of PP may improve the hyperphagia and hyperinsulinism seen in these animals. In obese humans, decreased, normal or increased, basal and stimulated concentrations of PP in plasma have been reported. However the advent of diabetes confounds the picture since PP levels in diabetes are generally raised. We have therefore examined the PP responses to intravenous secretin, a known PP secretagogue, in 23 obese subjects, 12 with normal and 11 with abnormal glucose tolerance, and compared the results with those in 23 age and sex-matched healthy controls. The mean maximum PP level in obese subjects with normal glucose tolerance (98 +/- 13 pg/ml) was significantly less than that in normal subjects (218 +/- 23 pg/ml) but in obese subjects with abnormal glucose tolerance, it was significantly greater (578 +/- 115 pg/ml). Within each of the 3 study groups taken separately, PP response to secretin was not correlated with glucose or insulin levels, or with the degree of obesity. Thus, obesity per se appears to be associated with impaired PP responses, which may be masked by abnormalities in glucose tolerance.