A total of 631 serum samples collected in 1969, 1979, and 1989 from adults and children were screened for Helicobacter pylori by Western blot analysis. Results showed that H. pylori seroprevalence has become less frequent over the 20-year period. By studying seropositivity by year of birth, the magnitude of a cohort effect of H. pylori seropositivity was estimated. The odds of being seropositive decreased by 26% per decade, P = .008 (95% confidence interval, 8%-41%). Estimates of seroprevalence adjusted for both age-specific variation and the cohort effect suggest that most seropositivity in adults occurs by the age of 15 years. The implication of these findings is that H. pylori infection is becoming less frequent and is predominantly acquired in childhood.