Changes in pancreatic polypeptide plasma concentrations have been reported in obesity. It has been suggested that altered PP plasma levels may play a role in the abnormal food intake observed in obesity. Earlier studies, however, have not considered the physiological fluctuations of PP during fasting. We examined PP plasma concentrations in 12 subjects with severe obesity and in 10 normal subjects during the entire cycle of interdigestive motility and after the administration of a standard mixed meal. Obese patients and healthy controls showed similar fluctuations of PP during individual phases of the migrating motor complex (MMC) and reached their peak PP plasma levels (134 +/- 35 (s.e.m.) pg/ml in controls vs 113 +/- 17 pg/ml in obese subjects) during phase III activity. Following the test meal, prompt release of PP occurred which was significantly higher than basal values at each 15 min interval during the first postprandial hour in both controls and obese patients. The integrated PP postprandial response at 60 min did not differ between obese patients (163 +/- 15 pg/ml.h) and controls (198 +/- 37 pg/ml.h; n.s.). A putative causal role for PP in obesity thus seems very unlikely.