Nutrients present in the ileum of humans can modulate endogenously stimulated pancreatic secretion. To determine whether cyclic interdigestive pancreatic secretion can also be influenced by nutrients in the ileum, six fasting volunteers were intubated with an oro-ileal multi-lumen tube for perfusing test and marker solutions, aspiration of duodenal contents and recording of motility. At the beginning of the interdigestive cycle, the ileum was perfused intermittently with solutions of carbohydrates, proteins or lipids in the physiological amounts observed in the ileum after a meal; saline solution was perfused as a control. After saline, protein and calcium perfusion, the expected periodic increase in chymotrypsin secretion was observed during phase II of the interdigestive cycle (p < 0.05 vs phase I). In contrast, carbohydrates and lipids inhibited the phase-II-associated increase in pancreatic secretion. These findings indicate that the ileum may be involved in the regulation of human interdigestive pancreatic secretion.