Malignant transformation of oral and bladder epithelia is often associated with loss of histo-blood-group-A- and -B-carbohydrate antigens, whereas these antigens, which are absent in normal adult distal colon (but present in fetal colon) reappear in malignant distal colon. In order to gain insight into the genetic basis of the biosynthetic regulation for these changes, we have correlated the expression of the A- and B-carbohydrate antigens with that of the A/B-gene-defined glycosyltransferases in colon, bladder and oral carcinomas by immunohistology. A newly developed anti-A/B-transferase monoclonal antibody (MAb) was used to demonstrate the in situ localization of transferase expression at the individual cell level with correlation to carbohydrate antigen expression, and gave the essential information that the transferase is derived from the ABO gene complex. The reappearance of A- and B-carbohydrate antigens in carcinomas of the distal colon was found to be unrelated to the expression of the A/B-transferase proteins, which were expressed throughout normal adult colon in accordance with previous enzymatic studies. In contrast, the loss of A- and B-carbohydrate antigens in malignant bladder and oral epithelia was accompanied by concordant loss of enzymes.