The effect of acute and long-term administration of cholestyramine, a non-absorbable bile salt binding resin, on exocrine pancreatic secretion, plasma-cholecystokinin (CCK) and plasma-pancreatic polypeptide (PP) was investigated in 10 healthy volunteers. Oral ingestion of 12 g cholestyramine augmented the stimulatory effect of a liquid test meal on plasma-CCK (3.5-fold) and plasma-PP (2-fold). During prolonged treatment with 3 x 12 g cholestyramine daily for 4 weeks, the most pronounced increase in basal hormone levels was observed after 1 day, but progressively decreased during treatment and had normalized after 4 weeks. However, the stimulated plasma-CCK output was still significantly elevated after cessation of treatment, compared with pretreatment values. After acute and chronic cholestyramine administration only stimulated lipase secretion was elevated, whereas trypsin and amylase remained unchanged. It is suggested that removal of bile salts enhances CCK and thereby PP release and pancreatic lipase secretion.