Because H. pylori is an enteric infection, its prevalence may be linked to exposure to other enteric pathogens. Results of observational studies on the association between H. pylori and gastroenteritis, however, have been conflicting. Some have shown increased incidence of diarrhea in children with H. pylori infection, with one study attributing 11% of diarrhea cases to H. pylori. Other studies found no association, and still others found a protective effect of H. pylori against gastroenteritis. Dissecting out confounding from true physiological associations can be difficult in observational studies. To better elucidate the association between H. pylori and gastroenteritis, we performed a direct challenge experiment with a well-characterized gastrointestinal pathogen, enteropathogenic Escherichia coli (EPEC). EPEC is a leading cause of infantile gastroenteritis in the world and has a long history of safe use in human experiments. It is also acid sensitive: in our laboratory less than 0.001% of inoculated EPEC organisms survived at pH 2.5. Our goal was to test the hypothesis that chronic infection with H. pylori increases the risk of diarrheal illness after direct challenge with EPEC.