BACKGROUND: Intraduodenal administration of lipids, through lipid digestion and release of cholecystokinin (CCK), induces viscero-visceral reflexes that affect gastric tone and sensitivity. It is unclear whether the same mechanisms control gastric function after an orally ingested meal. AIM: To evaluate the effect of orlistat, a selective lipase inhibitor, on gastric response to an orally administered meal. METHODS: Eighteen healthy volunteers participated in this study. They were treated for 5 days with orlistat (120 mg) or placebo t.d.s. in a double-blind randomized crossover design. During treatment, all subjects underwent a gastric barostat study, measurement of plasma CCK levels and a satiety drinking test. RESULTS: Although CCK plasma levels were significantly decreased, pre-treatment with orlistat failed to affect gastric compliance (72 +/- 6 mL/mm Hg and 64 +/- 6 mL/mm Hg, NS), gastric sensitivity (discomfort threshold 12.2 +/- 0.6 mm Hg vs. 10.9 +/- 0.6 mm Hg above minimal distending pressure, NS) or gastric accommodation (172 +/- 41 mL vs. 206 +/- 49 mL, NS) to an orally ingested meal. Furthermore, orlistat pre-treatment had no significant effect on the amount of calories ingested during a satiety drinking test (1329 +/- 88 kcal vs. 1217 +/- 115 kcal, NS). CONCLUSION: Administration of a lipase inhibitor does not affect gastric compliance, sensitivity to distension and accommodation to an orally ingested meal, and does not influence meal-induced satiety.