Background: Esophageal hypersensitivity is important in gastro-esophageal reflux disease (GERD) patients refractory to acid-suppressive therapy. Stress affects visceral sensitivity and exacerbates heartburn in GERD. Peripheral CRH is a key mediator of the gut stress response. We hypothesize that CRH increases esophageal sensitivity and alters esophageal motility in health. Methods: Esophageal sensitivity to thermal, mechanical, electrical and chemical stimuli was assessed in 14 healthy subjects after placebo or CRH (100μg IV). Perception scores were assessed for first perception, pain perception threshold (PPT) and pain tolerance threshold (PTT). Esophageal motility was investigated by high resolution impedance manometry, before and after CRH and evaluated by distal contractile integral (DCI) and intrabolus pressure (IBP). Pressure flow analysis assessed bolus clearance (impedance ratio), degree of pressurization needed to propel bolus onward (IBP slope) and pressure flow (pressure flow index, PFI). Stress and mood were assessed during the study. Results: Sensitivity to mechanical distention was increased after CRH compared to placebo (PPT p=0.0023; PTT p=0.0253). CRH had no influence on the other stimulations. DCI was increased for all boluses (liquid, p=0.0012; semi-solid, p=0.0017; solid, p=0.0107). Impedance ratio for liquid (p<0.0001) and semi-solid swallows (p=0.0327) decreased after CRH. IBP slope increased after CRH for semi-solid (p=0.0041) and solid (p=0.0003) swallows. PFI increased for semi-solid (p=0.0017) and solid swallows (p=0.0031). Conclusion: CRH increased esophageal sensitivity to mechanical distention, not to the other stimulation modalities. CRH increased esophageal contractility and tone, decreased LES relaxation, increased esophageal bolus pressurization, improved esophageal bolus clearance and increased pressure flow.