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Activated eosinophils can be identified by electron microscopy (EM) Previous studies have shown EM evidence of eosinophil activation in a variety of gastrointestinal conditions associated with inflammation. The purpose of this study was to evaluate the activation state by EM of duodenal mucosal eosinophils in children who presented with dyspepsia and to determine if eosinophils are activated in patients with normal eosinophil counts on routine histology.Twenty patients (ages 7–15 years) with dyspepsia were evaluated. All had normal gross endoscopies and Helicobacter pylori was excluded. Each patient had two endoscopic forceps biopsies taken from both the duodenal bulb (DB) and the second portion of the duodenum (DS) for routine histology to determine eosinophil counts. Two additional biopsies were taken from the adjacent mucosa of each site for EM evaluation. The eosinophil activation state was determined for each specimen and a degranulation index was calculated for DB specimens.On routine histology, peak eosinophil counts were greater than or equal to 20 per hpf in three patients, 11 to 19 per hpf in 12 patients, and less than or equal to 10 per hpf in 5 patients. All patients showed evidence of EM activation on DB specimens and 95% showed activation on DS specimens. The mean degranulation index was 50.5 + 12.0% with 65% of specimens revealing moderate (20 – 60%) degranulation and 30% of specimens revealing extensive (greater than 60%) degranulation.Eosinophils present in the duodenal mucosa of children with dyspepsia are activated in a significant proportion of patients, even in those with normal eosinophil counts. The degree of degranulation is similar to that seen in other conditions where eosinophils have a pathogenic role.