Discovered in 1982 as a cause of gastroduodenal ulceration, Helicobacter pylori (Hp) is the major cause of gastritides (e.g. chronic-active) and primary duodenal ulcers in adults and children. [Warren, 1983 #1180; Whitney, 2000 #1345; Ashorn, 1995 #1179; Asante, 1997 #1173; Drumm, 1987 #355; Czinn, 1986 #101; Drumm, 1988 #1096; Ernst, 2000 #1351; Goggin, 1998 #986; Torres, 2000 #1346] Infection with Hp, particularly in susceptible persons, is also strongly linked to gastric adenocarcinoma cancer and mucosal-associated lymphoid tissue-type (MALT) lymphomas. [Uemura, 2001 #1409; Alexander, 2000 #1232; Alm, 1999 #1038; Blaser, 1995 #757; Correa, 1990 #1523; El-Omar, 2000 #1272] The majority of infections worldwide are acquired in childhood. In the United States, minority populations (African Americans, Hispanics) have increased seroprevalence rates in all age groups. [Fontham, 1995 #139; Gold, 2001 #1422; Graham, 1991 #235; Staat, 1996 #190; Smoak, 1994 #618] Consensus guidelines for pediatric Hp infection were first published in 1999, yet there remains an overwhelming paucity of information regarding both the epidemiology of pediatric Hp infection and associated diseases. [Gold, 2000 #1347; Drumm, 2000 #1123; Sherman, 1999 #1129; Hunt, 1998 #353] It is not known why some Hp-infected children develop symptoms, and mechanisms accounting for differences in the inflammatory response and disease in Hp-infected children are uncharacterized. Using a multicenter study approach to test our hypothesis, this proposal will provide an in depth examination of the association between host factors, Hp strain genotype, and the severity of gastric inflammatory response in children. Variation between age, race/ethnicity, medical/environmental exposures, socioeconomic status and geographic regions and their effects on disease phenotype in children will be investigated. These studies will address unanswered questions about the earliest stages in the pathobiology of Hp infection that are essential to improve our ability to manage this infection in children, and potentially, identify and understand "at risk groups" to prevent more severe disease sequelae in adults. Understanding the evolution of the host response to Hp infection is needed to develop prevention strategies or new therapies, and allow a better definition of the pathobiology of this human pathogen that causes significant morbidity, suffering, and economic impact in our society.