Canine and human exocrine pancreatic secretion into the duodenum during fasting is cyclical and related to intestinal motility. To characterize the composition of pure pancreatic juice during the cyclically recurring sequence of propagated motor events (interdigestive motor complex) and to establish whether pancreatic reflux occurs, dogs were prepared with three permanent indwelling duodenal catheters and a pancreatodochal cutaneous catheter. The duodenal catheters were used to record duodenal pressures and measure pancreatic secretion of trypsin, lipase, and bicarbonate, based on the recovery of a constantly perfused marker, [14C]PEG. Pancreatic duct pressures or pancreatic juice concentrations of [14C]PEG, trypsin, lipase, or bicarbonate (done separately in each of five dogs throughout one interdigestive cycle on 4 different days) were related to duodenal motor activity. Finally, the pancreatic duct orifice of freshly sacrificed dogs was examined by light and electron microscopy. During fasting, (1) pancreatic volume secretion increased 10-fold during phases II, III, and IV (P less than 0.001), and bicarbonate concentration increased during phases III and IV (P less than 0.05) compared with phase I, while trypsin and lipase concentrations did not change; (2) reflux of duodenally perfused [14C]PEG into the pancreatic duct occurred in two of five dogs and was minimal (less than 0.1%); and (3) a positive mean pressure gradient from duodenum to pancreatic duct occurred only during phase III (7.4 +/- 4.1 cm H2O). Anatomic studies of the pancreatic duct opening showed a specialized papillary mucosa and an independent crescentic sphincter muscle. We conclude that during fasting, pancreatic juice composition is intimately linked to the different phases of interdigestive intestinal motor activity and that an efficient antireflux mechanism exists.