['We propose that regions outside the bioactive 7-amino acid carboxyl terminus of cholecystokinin (CCK)-58 influence its biological activity. Here we evaluate if sequence variation of the N-terminal regions of rabbit and canine CCK-58 changes their biological activities.', 'Cholecystokinin-like immunoreactivity was purified from rabbit intestinal extracts by reverse phase and ion-exchange high-performance liquid chromatography steps. The peptide was characterized by microsequence and mass spectral characterizations of the intact and tryptic peptides. Canine and rabbit CCK-58 were evaluated for their CCK1 and CCK2 receptor binding, receptor activation, and immunologic properties.', 'The sequence of rabbit CCK-58 differs from that of canine CCK-58 in 9 of the amino terminal 40 residues. Canine CCK-58 was approximately 3-fold more potent than rabbit CCK-58 for CCK1 receptor binding and CCK2 receptor binding, but about the same potency for stimulation of amylase release from purified acinar cells. The canine peptide was 9-fold more immunoreactive than rabbit CCK-58.'] Does sequence variation outside the `` active '' region of dog and rabbit cholecystokinin-58 result in bioactivity differences?