INTRODUCTION AND OBJECTIVE: Functional dyspepsia (FD) is a functional gastrointestinal disorder that affects a significant number of children presenting with chronic abdominal pain. A high proportion of these children undergo endoscopy to obtain mucosal biopsies which, by standard criteria, generally do not identify a clear explanation for symptoms. We undertook this study of children diagnosed with FD to elucidate the histopathological changes of gastroduodenal mucosa and to describe mast cell and eosinophil densities. METHODS: In this retrospective study, we evaluated 114 FD subjects and 10 control subjects from whom gastric antral and duodenal biopsies were available as formalin-fixed paraffin embedded tissue. We reviewed the H&E stained slides and performed immunohistochemistry for tryptase, to determine eosinophil and mast cell densities, respectively. RESULTS: We found that the duodenal mucosa showed no evidence of inflammation in 86% of subjects, a median peak eosinophil count of 24 and a median peak mast cell count of 22. The histopathological features of the gastric antral mucosa comprised no evidence of inflammation in 52% of subjects, mild chronic inflammation in 41% of subjects, a median peak eosinophil count of 11.5 and a median peak mast cell count of 18. CONCLUSIONS: A significant proportion of children with FD do not show chronic or active inflammation, but have increased mast cell density and eosinophil density in the stomach and duodenum mucosa. Our study adds functional dyspepsia to the list of various abnormalities that have increased gastroduodenal mucosal elevations of eosinophils and/or mast cells.