The histo-blood group ABO carbohydrate antigens are differentially expressed in epithelia in close correlation with cellular differentiation. In order to gain insight into the biosynthetic regulation of these carbohydrate antigens, we correlated the expression of A carbohydrate antigens with that of the A gene defined glycosyl-transferase by immunohistology of human oral epithelia using monoclonal antibodies. In glandular epithelium the A transferase was found in mucous cells similar to that of the A carbohydrate antigens. In stratified non-keratinized squamous epithelium the A transferase was expressed only in spinous cell layers, which is in accordance with the appearance of the A carbohydrate antigens in these more mature cell layers. This simultaneous acquisition of the primary and secondary gene product of a glycosyltransferase gene, provides evidence that the well-defined sequential expression of histo-blood group carbohydrate antigens in stratified squamous epithelium may be directly regulated at the transcriptional level of the glycosyltransferase. Future studies will address the mechanism behind loss of A antigens in premalignant lesions and carcinomas.