Helicobacter pylori seroprevalence levels in US adults participating in the continuous National Health and Nutrition Examination Survey (1999-2000) increased with age in all racial/ethnic groups, with significantly higher age-standardized levels in Mexican Americans (64.0%, 95% confidence interval (CI): 58.8, 69.2) and non-Hispanic blacks (52.0%, 95% CI: 48.3, 55.7) compared with non-Hispanic whites (21.2%, 95% CI: 19.1, 23.2). Although seroprevalence levels remained similar to those found in National Health and Nutrition Examination Surveys from 1988 to 1991 among non-Hispanic blacks and Mexican Americans, they were significantly lower in non-Hispanic whites, especially at older ages. The factors driving the decline in H. pylori seroprevalence appear to be acting preferentially on the non-Hispanic white population.