A luminal cholecystokinin releasing factor (LCRF), has been purified from intestinal secretion and found to have a mass of 8136 daltons. The amino-terminal 41 residues have been sequenced. Previous studies showed that intraduodenal infusion of the synthetic amino-terminal 35 amino acid peptide, LCRF1-35 significantly stimulated pancreatic protein and fluid secretion in conscious rats, but the peptide did not stimulate amylase release from isolated, dispersed pancreatic acini. In the present study, several fragments of LCRF were synthesized and tested for CCK-releasing activity (pancreatic protein secretion) to determine whether shorter fragments of LCRF exhibit the characteristic biological activity of native LCRF and synthetic LCRF1-35. Compounds tested were LCRF1-41, LCRF1-35, LCRF1-65 and LCRF11-25. Of the fragments shorter than LCRF1-35, only LCRF11-25 but not LCRF1-6 had significant CCK releasing activity. LCRF1-41 was equivalent to LCRF1-35 in potency and efficacy. Intravenous and intraduodenal infusion of LCRF1-35 elicited nearly identical dose-response curves.