Duodenogastric reflux may have pathophysiologic importance, but its mechanism is poorly understood. We propose that duodenogastric reflux and periodic changes in motor and secretory activity of the upper gut during fasting may be related. Therefore we determined the relationships between duodenogastric reflux and interdigestive motor-secretory cycles in a group of 6 healthy individuals, on each of whom we performed three 7-h studies in random order on separate days. In all studies gastric intubation and antral pressure recordings were performed. However, in design 1 we used a slow duodenal perfusion rate of [14C]PEG in saline (0.25 ml/min) while in design 3 we used a fast perfusion rate (3.0 ml/min). Duodenal pressures were also recorded during these designs. In design 2 no transpyloric tubes were present. Our study shows that, in humans, fasting duodenogastric reflux of bile and pancreatic juice is cyclic and closely related to the interdigestive migrating motor complex. Reflux is highest during late phase II (when secretory activity is also on the rise) and lowest after phase III. One of the important functions of the migrating motor complex in humans may be to clear the stomach of refluxed duodenal secretions.