To examine the association of Helicobacter pylori infection with adenocarcinoma of the stomach in Japanese patients, we studied 29 patients and 58 matched controls. Ascertainment of H. pylori status was based on the presence of specific IgG to H. pylori. For the entire group, an association of this infection with gastric adenocarcinoma was suggested but not statistically significant. For patients in a putatively high-risk subgroup (non-cardia tumors and age < or = 70 years), the association was significant. Assays detecting serum IgA to whole H. pylori cells and cytotoxin, IgG to cytotoxin and Hp54K (the heat-shock protein homolog) and serum neutralization of cytotoxin activity each showed clear differences between H. pylori-infected and uninfected persons in this population. However, for none of these assays was there a significant difference between values for H. pylori-infected persons with or without gastric cancer. Thus, while H. pylori infection was associated with non-cardia gastric cancer in Japanese persons < or = 70 years of age, use of these additional serologic markers did not define additional factors that might be associated with increased risk.