Incidence and mortality rates for gastric cancer in rural People's Republic of China differ greatly over short distances. In Shandong Province, we studied asymptomatic adult subjects from Bei Duan village (n = 196) in Linqu County (a high-risk area for gastric cancer) and from Shi Huang village (n = 192) in Cangshan County (a low-risk area for gastric cancer). The prevalence of advanced precancerous gastric lesions (APGL) was assessed by microscopic examination of endoscopic stomach biopsies. ELISAs were used to detect serum IgG to Helicobacter pylori whole-cell antigen and to the CagA protein. A logistic regression model was used to quantify the role of the two H. pylori seromarkers in explaining the differences in prevalence of APGL between the two villages after adjusting for age and sex. The prevalence of APGL was much greater in Bei Duan than in Shi Huang. Although H. pylori seroprevalence by the whole-cell ELISA was similar in the two populations, seroprevalence of CagA was significantly greater in Bei Duan. Although age, sex, and both H. pylori seromarkers were associated with APGL in the logistic regression model, the effect of village of residence remained strong after adjustment for all four covariates. Only a relatively small proportion of the difference in prevalence of APGL between these two rural Chinese populations can be explained by differences in H. pylori or CagA seroprevalence.