BACKGROUND & AIMS: 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 H. pylori seroprevalence among Swedish school children with varying family backgrounds. METHODS: In a cross-sectional study, 695 of 858 (81%) 10-12-year-olds in 36 school classes in Stockholm donated blood and answered a questionnaire. Infection was detected by enzyme-linked immunosorbent assay and confirmed by immunoblot and urea breath test. RESULTS: Overall, 112 (16%) children were infected. The seroprevalence was 2% among 435 children with Scandinavian parents and 55% among 144 children with origin in high prevalence areas (Middle East and Africa). Among children born in Scandinavia, the odds ratios (adjusted for gender, socioeconomic status, and family size) for being seropositive were 39.1 (95% confidence interval, 16.7-91.3) and 5.6 (1.8-17.3) when having parents born in high and medium prevalence areas, respectively, relative to children with Scandinavian parents. Importantly, the prevalence of infection among the classmates was not a risk factor for H. pylori infection. CONCLUSION: Our data indicate that intrafamilial transmission is far more important than child-to-child transmission outside the family. The H. pylori prevalence in the parental generation may be a crucial determinant for the child's risk of contracting the infection.