Blood donors are often used as proxies for the general population in studies of Helicobacter pylori epidemiology. Our aim was to test if the age-specific seroprevalence rates among blood donors match with the corresponding rates in a random population sample. This descriptive study was based on sera obtained from 3,502 blood donors representing all Swedish counties and cities. An age-stratified random population sample of 1,030 from Stockholm County served as comparison. Sera were analyzed by an in-house enzyme-linked immunosorbent assay for H. pylori immunoglobulin G antibodies. In the population sample, we found the expected increase with age in the seroprevalence of H. pylori infection. This was true also among young blood donors, while the prevalence-by-age curve showed a deflection downward among blood donors who are > 50 years of age. In this age group, the probability of being seropositive was reduced by 73% (95% confidence interval [CI], 63 to 81%) relative to the population sample. Overall, the adjusted odds ratio for H. pylori seropositivity among blood donors was decreased by 43% (95% CI, 28 to 55%). Thus, it appears that blood donors who are H. pylori seropositive selectively disappear from the blood donor cohort. We speculate that H. pyloriseropositive blood donors may tolerate repeated bleedings less well than do noninfected individuals and/or that the general well-being among those who are infected may be somewhat impaired. Our unexpected observation indicates that blood donors may be less suitable as proxies for the general population in analytic studies of H. pylori infection and that the underlying cause needs further study.Helicobacter pylori is accepted as a principal cause of nonautoimmune chronic gastritis (10). Moreover, eradication of H. pylori prevents recurrence of peptic ulcers (14), and evidence for a causal role in gastric cancer is accumulating (11,17,30).H. pylori infections are mainly acquired in early childhood (13). In developing countries, the seroprevalence of the infection is higher than in developed countries, where it rises gradually with age (12,23). This latter phenomenon is considered to reflect a birth cohort effect. Hence, the higher infection prevalence in older individuals represents higher childhood infection rates in these birth cohorts rather than acquisition during adult life (1, 9).In European epidemiological studies, blood donors are often used to represent the general population since all European countries have unpaid donors (34, 36). The appropriateness of this assumption has not been rigorously tested for H. pylori seroprevalence.We took advantage of a large nationwide sample of blood donors, drawn for the purpose of investigating the seroprevalence of Borrelia burgdorferi infection in different parts of Sweden (28), to study also the age-specific seroprevalence of H. pylori infection, presuming that the blood donors were representative for the general population. We then compared the seroprevalence pattern among blood donors with that in a population contr...