Seven healthy volunteers were intubated with two double lumen nasogastric tubes, one in the stomach, the other in the duodenum. This system allows simultaneous sampling of gastric juice and separate intraduodenal perfusion with a dietary fat (fish oil, 1269 kJ). Gastrin-17 was infused i.v. at a rate of 40 pmol/kg/h throughout the study. Gastric lipase was measured at 15-min intervals as activity (tributyrin) and as immunoreactivity (ELISA). Infusion of gastrin-17 resulted in a stable increase in the plasma concentration from a basal concentration of 8.3 +/- 0.8 pmol/l to 41.4 +/- 4.2 pmol/l. Perfusion with fat reduced gastric lipase activity from 24.2 +/- 5.3 to 7.2 +/- 2.5 kU/l (P < 0.05), and immunoreactivity from 0.7 +/- 0.1 to 0.42 +/- 0.1 mg/l (P < 0.05). After termination of fat perfusion, gastric lipase secretion increased again, though not reaching preinhibitory concentrations. During the intraduodenal perfusion with fat the plasma concentrations of glucagon-like peptide-1 (GLP-1) and cholecystokinin (CCK) increased from 6.9 +/- 0.5 to 15.1 +/- 1.5 pmol/l (P < 0.05) and from 1.2 +/- 0.4 to 3.8 +/- 0.9 pmol/l (P < 0.05). This study reveals a negative effect of fat in the duodenum on gastric lipase secretion. This effect may be mediated by GLP-1 and/or CCK.