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Gastroduodenal disease is more common among adults and children with cagA+ Helicobacter pyloriinfection, but disease severity varies among those infected with cagA+ strains. We examined whether cagAin situ expression can predict disease manifestations among H pylori–infected children. Fifty‐one children were selected from 805 patients with abdominal symptoms who underwent esophagogastroduodenoscopy with gastric biopsies. Endoscopic and histologic gastritis were scored and H pyloricolonization was quantified by Genta stain and in situ hybridization expression of 16S rRNAand cagA. Endoscopy was either normal (n = 14) or demonstrated nodularity (n = 18), gastric ulcer (n = 8) or duodenal ulcer (n = 11). H pyloriwas present in 7, 18, 6, and 10 children, respectively. Expression of 16S rRNAand cagAwere significantly higher in children with ulcer compared with normal children. The fraction of H pyloribacteria expressing cagAin situ was higher in children with ulcer compared to those with endoscopic nodularity (P< 0.05). Thus, cagAin situ expression is increased in H pylori–infected children with peptic ulcers and may play a role in the pathogenesis of peptic ulcer disease during childhood. Determination of in situ expression of cagAcomplements traditional isolation and in vitro testing of single‐colony isolates.