Eosinophilic esophagitis (EE) is a recently recognized disorder characterized by the accumulation of eosinophils in the esophagus. Symptoms of EE frequently mimic those of gastroesophageal reflux disease, but the 2 diseases are quite distinct in terms of the histopathology and response to therapy. We demonstrate that EE involves the interplay of numerous genes, especially the eosinophil chemoattractant eotaxin-3, allowing molecular distinction from other forms of esophagitis and consideration of targeted therapeutic intervention.