Recent studies have demonstrated common cortical activity regions associated with esophageal acidification and swallowing. The effect of sensory signals imparted on these regions by esophageal acidification on swallow-related brain activity has physiologic and clinical ramifications. Aim: Determine the effect of prior, unperceived esophageal acid exposure on cortical activity associated with swallowing. Methods: fMRI techniques monitored brain activity associated with volitional swallowing before and after subliminal esophageal acid stimulation. Studies were carried out in two phases. In phase one (15 healthy, right-handed subjects, age 21-49 years, 7F) using whole brain imaging, we documented the potentiating effects of esophageal acidification on swallow-related cortical activity. In phase two (10 healthy, right-handed subjects, age 20-54 years, 5F) using high resolution functional MR imaging, we measured swallow-induced regional brain activity within the cortical swallowing network before and after esophageal acidification. Due to constraints imposed by high resolution MRI for region-of-interest (ROI) analysis, we studied only the left hemisphere in this phase. Results: None of the subjects developed heartburn during acid perfusion. Phase One: The number of swallow-induced activated voxels increased by 43% following esophageal acid stimulation. (pre-acid: 44±3 voxels, post-acid: 63±6 voxels, mean±SEM, p< 0.05) Phase Two: Contrary to saline perfusion, ROI analysis showed significantly increased regional swallow-related fMRI activity volumes as well as percent maximum signal change after esophageal acid perfusion in cingulate, prefrontal, insula and sensory/motor regions (p<0.05). The precuneus showed no significant change. Conclusions: Subliminal esophageal acid stimulation has a potentiating effect on the cortical swallowing network in healthy individuals.