Studies of the pattern of change in the epidemiology of Helicobacter pylori infection are scarce. A longitudinal cohort study consisted of 644 children and adults, and two independent cross-sectional surveys were conducted in rural Japan between 1986 and 1994. The anti-H. pylori IgG seroconversion rates were 1.1% and 1% per year for children and adults, respectively. The seroreversion rate per year was 1.8% for children and 1.5% for adults. The cohort study was confirmed by the two cross-sectional studies. H. pylori prevalence fell in all age groups in both children (odds ratio [OR] = 0.5, 95% confidence interval [CI] = 0.2-1.0, P = .05) and adults (OR = 0.4, 95% CI = 0.3-0.6, P = .001). The rate of loss of H. pylori infection was greater than the acquisition. Data regarding acquisition and loss of H. pylori infection are critical to understanding the epidemiology of the infection and to developing treatment and vaccination strategies.