Fifty esophageal adenocarcinomas were investigated for their expression of Le(a), Le(x), and Le(a)-Le(x). Among the 50 adenocarcinomas, 17 cases developed in Barrett's epithelium. Those 17 differed from the other 33 cases by expressing much less Le(x). Fifty-nine percent of Barrett's adenocarcinomas were Le(x) negative compared with 24% of the non-Barrett's carcinomas. All Barrett's adenocarcinomas showed less than 50% Le(x) whereas 50% of non-Barrett's carcinomas showed between 50 and 100% expression. The statistical correlation coefficient for this association was P < 0.001. Normal gastric cardia epithelium showed the same Le(x) expression in both groups. In the Barrett group, Le(x) expression decreased from normal through intestinal metaplasia and dysplasia to adenocarcinoma. This progression was not seen in the non-Barrett group. Loss of Le(x) expression may prove useful in following patients with Barrett's epithelium in evaluating progression toward a malignant process. No difference in expression of Le(a) and Le(a)-Le(x) was found between Barrett's and non-Barrett's carcinomas.