Immunohistochemical staining showed an aberrant expression of Le(a) antigen in the intestinal metaplastic glands of the gastric mucosa of secretors, as reported by others. In this study, we have demonstrated for the first time that the Lewis enzyme is well colocalized with Le(a) antigen, indicating that the Lewis enzyme is responsible for Le(a) antigen synthesis in the gastric mucosa. The staining intensity of the Lewis enzyme was much stronger in the cells with intestinal metaplasia than the cells without metaplasia, regardless of the secretor status. The amount of transcript of the Lewis gene was related to the degree of metaplasia; i.e., the more severe the metaplastic change was, the more abundantly the transcripts of the Lewis gene were expressed. This augmentation of the Lewis enzyme in metaplastic tissues was also confirmed by Western blotting analysis using a specific antibody against the Lewis enzyme. We conclude that intestinal metaplastic change of gastric mucosa is usually accompanied by a marked augmentation of the Lewis enzyme expression, which results in the enhanced expression of Le(a) antigens, particularly in secretors.