There are few observations of in vivo pancreatic secretory changes that accompany acute pancreatitis. We hypothesized that acute pancreatitis impairs pancreatic exocrine function. We developed a conscious-rat experimental preparation with gastric, duodenal, bile, and pancreatic fistulas. We studied cholecystokinin-stimulated pancreatic secretion in conscious rats before and after inducing acute pancreatitis with supramaximal administration of caerulein--5 micrograms/kg/hr intravenously for 6 hours. Marked hyperamylasemia developed in all rats immediately after administration of caerulein. Basal and cholecystokinin-stimulated pancreatic juice flow and protein (enzyme) secretion decreased significantly 24 hours after acute pancreatitis was induced even though plasma amylase returned to basal levels. We conclude that acute pancreatitis markedly impairs pancreatic secretion.