Several prospective studies have shown a significant association between Helicobacter pylori seropositivity and the risk of gastric cancer. Only a small proportion of H. pylori-infected individuals will, however, develop gastric cancer, and it is unclear what effects other factors, such as diet, might have on the risk of cancer. Eighty-seven subjects with gastric cancer were identified during the first 6 years of follow-up (mean 2.4 years) of a cohort of middle-aged men from Shanghai, China. They were matched with 261 cancer-free controls, and serum samples from all subjects, obtained at recruitment, were assayed for anti-H. pylori IgG antibodies. Questionnaire data provided information on a wide range of socio-demographic life-style and dietary variables. H. pylori seropositivity rates in the cases and controls were 54% and 56%, respectively. Neither the overall risk of developing gastric cancer nor the risk of developing non-cardia gastric cancer was significantly associated with prior M. pylori seropositivity. Adjustment for any of the other medical, dietary or life-style variables studied had little effect on the risk of developing non-cardia gastric cancer; simultaneous adjustment for all of these factors yielded an odds ratio of 1.17. The results do not support the hypothesis that H. pylori plays a role in the process of gastric carcinogenesis in China. It is possible that this is an artefact resulting from the relatively short follow-up period to date.