The exocrine pancreatic function of 8 patients with chronic adrenocortical insufficiency was studied and compared with 12 control subjects. The secretion of bicarbonate, lipase, and chymotrypsin in response to secretin and caerulein was significantly reduced in patients with adrenocortical insufficiency. The mean reduction in bicarbonate, lipase, and chymotrypsin output compared with the control values was 42%, 66%, and 53%, respectively. Chronic glucocorticoid substitution therapy restored pancreatic function almost to normal. It is concluded that the adrenal cortex plays an important role in maintaining the function of the exocrine pancreas in humans. The possible mechanisms are discussed.