A panel of monoclonal antibodies (MoAbs) against BGAg A, B, and H and Lewis a, b, X, and Y (Le a, Le b, X, Y) was used to characterize and evaluate the blood group antigens (BGAg) immunohistochemistry in Barrett's esophagus (BE) and associated adenocarcinomas (ACA). Thirteen cases of ACA arising in metaplastic columnar epithelium of the distal esophagus were reviewed (12 men; 1 woman; mean age: 59). Twelve cases had juxtaposed BE of different types with low-grade dysplasia in five and high-grade dysplasia in three. ACAs were classified as well differentiated (one case), moderately differentiated (three cases), and poorly differentiated (four cases). Five cases had mixed features. Loss of BGAg H was recorded in four ACA and in one adjacent BE. Loss of BGAg B was noted in three ACAs, but in only one case in the adjacent BE. Incompatible expression of BGAg A and B was present in one case each. Anomalous expression of Le a was seen in seven ACAs and adjacent BE. Loss of Le b was noted in six ACAs. Deletion of X was seen in four ACAs and in BE. Loss of Y was present in the only nonsecretor patient. We conclude that significant alterations of BGAg occur in BE and in associated ACAs. Recognition of these antigenic alterations warrants further investigation to define a role for BGAg immunohistochemistry in the surveillance of BE patients at risk of developing ACA.