The effects of Peptide YY (PYY) on pancreatic and intestinal growth have been investigated in conscious rats. Male Wistar rats equipped with jugular vein cannulas were randomly assigned to five groups. All rats received continuous i.v. infusion of gut peptides for 4 days, rats were then killed, and the pancreas and intestine were analyzed. Infusion of PYY alone at the dose of 400 pmol/kg.h affected neither pancreatic weight, DNA and RNA contents, or the duodenal weight, protein, DNA and RNA contents. Infusion of caerulein at the dose of 0.25 microgram/kg.h significantly increased pancreatic weight, DNA, RNA, and protein contents by 202%, 109%, 171%, 183% above control values, but it did not affect duodenal weight, DNA, RNA, and protein contents. PYY, 400 pmol/kg.h, infused simultaneously with caerulein significantly reduced by 39%, 35%, and 45% increases in pancreatic weight, RNA and DNA contents stimulated by caerulein, respectively. Surprisingly, administration of PYY antiserum also resulted in a small but significant reduction in caerulein-stimulated pancreatic weight, protein, and DNA contents. In conclusion, PYY has an inhibitory effect on cholecystokinin-stimulated pancreatic growth and may play a physiological role as an inhibitor of pancreatic growth.