The effect of cholecystokinin (CCK) on the pancreas was investigated in the pig in two experiments. Fifteen pigs were fed a diet containing 17 or 48% protein with or without MK329 (4.5 mg per meal). MK329 enhanced the postprandial peak of plasma CCK during the first 30 min, but pancreas adaptation to high protein was not affected. Sixteen pigs were divided into two groups: 12 pigs were infused with CCK-8 + secretin for 1 h and four pigs received a standard meal. In both groups, pancreatic secretion tests were performed under infusion of the vehicle alone or with MK329. After CCK + secretin, MK329 (65-500 CLg/kg/h) did not alter CCK plasma levels and reduced the early pancreatic protein response by about 30%. Enzyme outputs in pancreatic juice were modestly affected by MK329. After the meal, MK329 (500 mu g/kg/h) doubled the postprandial peak of plasma CCK and lowered the pancreatic protein output by 35-40% for the first 30 min. We suggest that (a) pancreatic adaptation to high dietary protein is not mediated via CCK-A receptors and (b) the stimulation of pancreatic protein secretion by a meal or by exogenous CCK-8 is mediated partly by CCK-A receptors.