We have studied the effect of secretin (2U/kg as an intravenous bolus) upon the immunoreactive human pancreatic polypeptide (IRHPP) components, present in plasma from control subjects and from patients with multiple endocrine adenomatosis type 1.After secretin injection, plasma IRHPP increased significantly in both groups.Four IRHPP plasma components of >20,000, 10,000, 4,200 and 2,000 daltons were detected in all cases.The post-secretin plasma IRHPP increment was due to an increase in the l0,000-and 4,200-dalton components, suggesting that both components are secreted by the pancreatic polypeptide (PP)-cell.These data provide additional evidence to consider the IRHPP plasma component of 10,000 daltons as a co-secretory product of the PP-cell, and it may correspond to the described PP-precursor.