To assess the possible clinical utility of the C-terminal CCK-OP as a stimulus to exocrine and endocrine pancreatic secretin and gallbladder contraction in man, we administered increasing doses of CCK (0.066, 0.125, 0.25, and 0.5 CHR U/kg/hr) and CCK-OP (20, 40, 80, and 160 ng/kg/hr) in random order by constant intravenous infusion to six healthy volunteers. Standard intestinal perfusion methods were used, and duodenal outputs of lipase, trypsin, bicarbonate, and total bile acids and plasma levels of HPP were measured. CCK-OP, in a dose of 40 ng/kg/hr given simultaneously with intravenously administered secretin, produced maximal pancreatic enzyme secretion and gallbladder contraction, comparable to that induced by CCK. CCK-OP plus secretin produced only small increases in plasma HPP levels, whereas values after all doses of CCK were significantly higher (p < 0.05) and were similar to values caused by a meal. We concluded that the combination of intravenous CCK-OP (40 ng/kg/hr) plus secretin (0.25 U/kg/hr) should be an accurate and relatively inexpensive test of exocrine pancreatic function and gallbladder contraction in man. Further, an undefined component of 20% CCK is a potent stimulus for HPP release.