Helicobacter pylori infection is mainly acquired in early childhood but the exact routes of transmission remain elusive. To distinguish between risks of intrafamilial and extraneous child-to-child transmission we studied the seroprevalence of Helicobacter pylori among 10-12-year-old Swedish school children with varying family background. In a cross-sectional study, 695 children (81% of all invited) in 36 school classes in southern Stockholm donated blood and answered a structured questionnaire together with their families. Infection was detected by ELISA, and confirmed by immunoblot and urea breath test. Overall, 112 (16%) of the children were H. pylori infected. Seroprevalence was 2% among 435 children with Scandinavian parents and 55% among 144 children with at least one parent born in a high prevalence area (Middle East and Africa), indicating that the prevalence of H. pylori infection in the parental generation is a crucial determinant of the child's risk of infection. Importantly, the prevalence of infection among classmates was not a risk factor for H. pylori infection when family background was taken into account. In conclusion our data indicate that intrafamilial transmission is far more important than child-to-child transmission outside the family in a western society.