Alterations in the serum concentration of transforming growth factor a-1 (TGFa1) have been observed in gastric cancer patients. No study, however, has ever examined the association between the serum TGFa1 level and stomach cancer prospectively. We conducted a prospective, nested case-control analysis among apparently healthy men and women who were followed for up to 8 years in the JACC Study to assess whether serum level of total TGFa1 is associated with a subsequent risk of stomach cancer. The concentration of serum TGFa1 in previously collected blood samples was analyzed by ELISA for 209 individuals in whom a diagnosis of stomach cancer was documented, and for 409 controls matched with them for gender, age and study area. Baseline blood levels of TGFa1 were not related to the risk of stomach cancer in either men or women, a finding unchanged even after adjustment for potential confounders. The multivariate-adjusted odds ratio of stomach cancer in men and women was 1.10 (95% CI, 0.82 to 1.48) and 1.09 (95% CI, 0.80 to 1.48), respectively, for each increase of 1 SD in the TGFa1 value. In conclusion, serum TGFa1 levels were not associated with increased risks of subsequent stomach cancer.