Modest elevations in pancreatic polypeptide (PP) have been observed during exercise while fasting. To determine whether the PP response to a meal is similarly affected by exercise, seven healthy subjects were studied on two occasions. First, the postprandial PP response was determined during rest and then compared to a meal which was subsequently followed by a 45 min period of moderate exercise. Postprandial exercise significantly (P less than 0.01) enhanced the plasma PP response to peak levels of 182 +/- 22 pM versus 85 +/- 22 pM at rest. Concomitantly the plasma glucose fell to a nadir of 84 +/- 4 mg/dl which was significantly (P less than 0.01) below the rest level of 129 +/- 8 mg/dl. Although the rise in PP paralleled the fall in glucose, there was little relationship (r = 0.27) between the incremental changes in these two parameters. Thus, exercise is a natural setting which augments the plasma PP response to a meal. The mechanism may be related to the enhanced cholinergic vagal activity associated with the attendant fall in glycemia.