Catheter-based high-frequency intraluminal ultrasound imaging is a powerful tool to study esophageal sensory and motor function and dysfunction in vivo in humans. It can be combined with manometry, pH, and impedance measurement techniques to determine the relationships between different physiologic parameters. High-frequency intraluminal ultrasound imaging has provided a number of important insights regarding the longitudinal muscle function of the esophagus. On the basis of the ultrasound images and intraluminal pressure recordings, it seems that there is synchrony in the timing and the amplitude of contraction between the circular and longitudinal muscle layers. A sustained contraction of the longitudinal muscle layer is temporally related to esophageal chest pain and heartburn. The biomechanics of the esophageal wall and its relationship to sensory and motor function can be studied in humans in vivo by using high-frequency intraluminal ultrasound much more precisely than has previously been possible. Achalasia, diffuse esophageal spasm, and nutcracker esophagus are associated with hypertrophy of circular and longitudinal muscle layers. Finally, high-frequency intraluminal ultrasound imaging is the only technique that can detect reflux-related distention of the esophagus and its role in esophageal symptoms. Future approaches to display and quantify ultrasound image data are discussed. The principles of high-frequency intraluminal ultrasound described here are also applicable to study of the motor and sensory function of the other regions of the gastrointestinal tract.