A 10-week-old, male German shepherd dog was presented with a primary complaint of episodic ptyalism, dysphagia, vomiting, and mandibular salivary gland enlargement. An esophagram with fluoroscopy showed normal pharyngeal and esophageal function; however, upper gastrointestinal endoscopy and cervical ultrasonography revealed a focal circumferential thickening of the midcervical esophageal muscular wall, consistent with esophageal spasm. The puppy responded dramatically and completely to phenobarbital treatment. An unusual syndrome of phenobarbital-responsive hypersialosis was consistent with this dog's clinical presentation and the finding of apparent esophageal spasm. The pathogenesis of this syndrome is unclear, but it may represent a form of limbic epilepsy or peripheral autonomic dysfunction.