Following ingestion of a meal, unabsorbed nutrients may reach the distal intestine partly after the termination of the prandial period, i.e., in the presence of interdigestive motor and secretory patterns. To determine if interdigestive motility and pancreatic enzyme secretion are modulated by the delivery of nutrient into the ileal lumen, six fasting volunteers were intubated with an oroileal multilumen tube system that permitted multiple small intestinal manometry, gastric and duodenal aspiration, and perfusions of marker and test solutions. Ileal perfusions of nutrient or saline solutions were started during phase I of the interdigestive motility cycle. Ileal perfusion with carbohydrate or lipids increased the duration of motor quiescence and decreased the length of the interdigestive cycle, mainly by decreasing the proportion of phase II activity compared with ileal saline (p < 0.01). Pancreatic outputs of amylase, trypsin, and chymotrypsin prior to ileal perfusions were low because, due to the protocol, perfusions were started during phase I. With ileal saline, enzyme outputs increased (p < 0.05) in association with the occurrence of phase II motility, as expected. By contrast, ileal carbohydrate and triglyceride perfusion prevented the phase II-associated increase in enzyme outputs (p < 0.05). The data suggest that the presence of nutrients within the ileal lumen may modulate interdigestive motor and pancreatic functions.