Previously we demonstrated that postprandial duodenal pressure transiently exceeds pancreatic duct pressure in the dog. To determine whether this presure gradient causes reflux from the duodenum into the pancreatic duct, we provided each of five dogs with a permanent pancreatodochal catheter and three indwelling duodenal cutaneous catheters. 14C-PEG was infused through the proximal duodenal catheter; intraluminal pressures were monitored through the middle catheter at the level of the pancreatic duct orifice; and 15 cm abroad, duodenal contents were recovered from the third catheter. Fifteen-minute pooled samples were collected 1 hr preprandially and 2 hr postprandially from the pancreatic duct and duodenum and were analyzed for volume, lipase activity, and marker concentration. Reflux of duodenal contents occurred only in 10.8% of fasting periods but was observed in 38% of postprandial periods (p < 0.05). The total volume of duodenal content refluxed per 15 min approximated 0.1 ml and represented between 0.5% and 1% of total pancreatic volume flow and between 0.05% and 0.07% of total duodenal volume flow. Thus we have provided evidence that small amounts of duodenal contents may reflux into the pancreatic duct of dogs in our experimental model. This finding may be relevant to the pathogenesis of pancreatitis and pancreatic cancer.