Mast cells are believed to contribute to development of eosinophilic gastrointestinal disorders (EGIDs). We quantified mast cells and eosinophils in biopsies from patients with EGIDs and without known esophageal or gastrointestinal disease to investigate associations between these cell types and EGID and its features.We conducted a retrospective study of patients with EGID (n=52) and of children and adults who underwent upper endoscopy and were found to have no evidence of gastrointestinal or systemic conditions (n=123). We re-reviewed archived gastric and duodenal biopsies to quantify mast cells (by tryptase immunohistochemistry) and eosinophils. We calculated the specificity of cell count thresholds for identification of patients with EGIDs and evaluated the correlation between mast cell and eosinophil counts and clinical and endoscopic features.In the gastric biopsies from patients without esophageal or gastrointestinal diseases, the mean mast cell count was 18.1±7.2 cells/higher-power field (hpf) and the peak mast cell count was 21.9±8.2 cells/hpf. In the duodenal biopsies from patients without esophageal or gastrointestinal diseases, the mean mast cell count was 23.6±8.1 cells/hpf and the peak mast cell count was 28.1±9.3 cells/hpf. Mean and peak eosinophil counts in gastric biopsies from patients without disease were 3.8±3.6 eosinophils/hpf and 5.8±5.0 eosinophils/hpf; mean and peak eosinophil counts in duodenal biopsies were 14.6±8.9 eosinophils/hpf and 19.5±11.0 eosinophils/hpf. A mean count of 20 eosinophils/hpf in gastric biopsies or 30 eosinophils/hpf in duodenal biopsies identified patients with EGIDs with high specificity. Gastric and duodenal biopsies from patients with EGIDs had significant increases in mean mast cell counts compared to biopsies from patients without EGIDs. There was a correlation between mean mast cell and eosinophil counts in duodenal biopsies (R=0.47; P=.01). Mean mast cell and eosinophil counts did not correlate with symptoms or endoscopic features of EGIDs.We identified thresholds for each cell type that identify patients with EGIDs with 100% specificity. The increased numbers of mast cells and eosinophils in gastric and duodenal tissues from patients with EGIDs supports the concept that these cell types are involved in pathogenesis. However, cell counts are not associated with symptoms or endoscopic features of EGIDs.