Background/Aims: Cholecystokinin (CCK) administration has been shown to reduce lower esophageal sphincter (LES) pressure in normal subjects in manometric studies. Functional luminal imaging probe (FLIP) panometry offers a method to assess esophageal motility in response to sustained distension though mechanisms related to this response remain unexplored. The aim of this study is to evaluate the effect of CCK-8 on the esophageal response to distension in asymptomatic volunteers using FLIP. Methods: Esophageal response to distension was studied in 7 asymptomatic volunteers (mean age ± SD [27 ± 2]; 86% female) before and after CCK-8 administration in a crossover study design. During sedated endoscopy, FLIP was performed twice with CCK-8 administered via intravenous push in one of 2 protocols: during filling (n = 4) or during emptying (n = 3). Esophagogastric junction distensibility index (EGJ-DI) at 60 mL fill volume and esophageal body contractile response patterns were analyzed. Results: During the baseline FLIP study, all subjects had a contractile response with repetitive antegrade contractions both before and after CCK-8 administration. However, a sustained LES contraction or a sustained occluding contraction with esophageal shortening was observed in all subjects in the filling protocol, but in none during the emptying protocol. EGJ-DI was similar before and after CCK-8 during both filling (4.7 ± 1.9 mm2 /mmHg vs 4.3 ± 1.8 mmmm2 /mmHg) and emptying protocol (7.5 ± 1.4 mmmm2 /mmHg vs 6.9 ± 0.6 mmmm2 /mmHg). Conclusion While EGJ-DI appeared unaffected by CCK-8 administration in asymptomatic volunteers, CCK induced spastic-reactive contractions of the LES during distention suggesting that exogenous CCK interferes with normal LES relaxation during secondary peristalsis.