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Aim: The hypothesis that colonization with cagA(+) Helicobacter pylori strains protects against the development of gastroesophageal reflux disease (GERD) and its complications is tested., Methods: Patients with reflux esophagitis and Barrett's esophagus were studied. Antral biopsy specimens were obtained for detection of H. pylori. A serum sample was obtained for determination of IgG antibodies to H. pylori and to the CagA protein., Results: 736 patients were studied. 118 patients had reflux esophagitis, 36 had Barrett's esophagus, 108 had hiatal hernia without signs of inflammation (the reflux group), and 20 patients had esophageal or stomach cancer. The remaining 454 patients had no signs of GERD. The 262 patients with reflux disease had a significantly lower prevalence of H. pylori (34.9%) than the 454 controls (54.6%; p<0. 001). Among 310 H. pylori-positive patients from whom serum was available, colonization with cagA(+) strains was detected in 59% in the control group versus 35% in the reflux group (p<0.001)., Conclusion: Patients with reflux esophagitis and Barrett's esophagus have a significantly lower prevalence of H. pylori colonization than controls, in particular of the cagA(+) type. These data suggest that colonization with cagA(+) H. pylori strains may be protective against the development of GERD, (Copyright 2000 S. Karger AG, Basel.)