The relationship between gastric Helicobacter pylori colonization and esophagitis was determined in 457 children undergoing endoscopic evaluation of abdominal pain and/or vomiting. In all patients, biopsies of the esophagus were examined histologically, and two antral biopsies were analyzed for the presence of H. pylori, using standard microbiological and histochemical techniques. The incidence of biopsy-proven esophagitis was similar in H. pylori-positive (15/56 patients) and -negative (94/401; p = NS) groups. Clinical improvement, after 2 months of antisecretory therapy with H2-receptor antagonists, was independent of H. pylori status (11/15 vs. 68/94 responders; p = NS). All 26 H. pylori-negative nonresponders became asymptomatic with a second course of H2-blockers. The 4/15 H. pylori-positive patients (all of whom had associated gastritis/duodenitis) who failed antisecretory therapy responded clinically to treatment with amoxicillin plus bismuth subsalicylate. These data indicate that primary treatment of biopsy-confirmed esophagitis in children should include anti-secretory agents, regardless of H. pylori status. A small percentage of H. pylori-positive patients with esophagitis and concomitant gastroduodenal inflammation may require additional antibacterial therapy, suggesting that presence of the organism should be assessed in all pediatric patients undergoing upper endoscopic evaluation.