The ability of newborns to digest proteins, fats, and carbohydrates depends, to a large extent, on their level of exocrine pancreatic function. Building on the limited published data, we studied pancreatic enzyme activities in the duodenal fluid and the response of the exocrine pancreas to secretogogues in 15 premature and full-term infants at birth and at 30 days of age. We compared these findings to those obtained from identical studies of 17 children age 2 years and above. In addition, we measured the pancreatic exopeptidase, carboxypeptidase B, in relation to other pancreatic enzymes. The duodenal fluid of newborns and infants contained no amylase and negligible lipase. Carboxypeptidase B levels were also low compared to those in the older children. In contrast, chymotrypsin activity in infants was about 50% to 60% of level found in the older children. Trypsin activity, the highest of all the enzymes measured, was about the same in both newborns and older children, with a transient increase at 30 days. Administration of pancreozymin had no effect on pancreatic enzymes in the duodenal fluid of newborns and a slight effect on 1-month-old infants. But by age 2 years, a full response of the pancreas to pancreozymin was evident. In infants and newborns, responses to secretin were poor. Thus, the secretory response of the human pancreas to secretogogues, absent or minimal at birth, is acquired during the postnatal period.