Ethanol is often implicated in the pathogenesis of acute pancreatitis, but the pathophysiologic processes of alcohol-induced acute pancreatitis remains poorly understood. We found that ingestion of alcohol by healthy volunteers did not stimulate release of cholecystokinin, which is the chief hormonal stimulant of pancreatic enzyme secretion, nor did it significantly alter fasting levels of pancreatic polypeptide, a hormonal inhibitor of pancreatic enzyme secretion. In conscious dogs prepared with chronic pancreatic fistulas, direct intraduodenal instillation of ethanol significantly reduced pancreatic protein output, and this reduction corresponded to a decline in plasma concentrations of cholecystokinin that was similar in the percentage of diminution and in duration. These data suggest that, in patients who do not have chronic pancreatitis, alcohol does not induce acute pancreatitis, either by stimulating cholecystokinin release or by stimulating enzyme secretion directly.