Monoclonal antibody (MAb) B72.3 detects an epitope carried by high-molecular-weight mucins (tumor-associated glycoprotein, TAG-72) recently identified as sialyl-Tn. B72.3 MAb has a restricted pattern of reactivity with normal tissues but it reacts with a high proportion of epithelial cancers. To determine the possible relationship between neoplastic transformation and reactivity with B72.3 MAb, we have analyzed samples of normal colon, colon cancer and transitional mucosa (mucosa adjacent to colorectal cancer) or reactive mucosa (mucosa adjacent to squamous carcinoma of the anal canal, or mucosa overlying lymphoma). B72.3 MAb reacted strongly with 21/21 specimens of transitional mucosa and with 17/21 specimens of adjacent colon cancer. Reactivity of B72.3 MAb with transitional mucosa was strong and homogeneous, whereas reactivity with cancer tissue was weaker and more heterogeneous. Reactive mucosa adjacent to squamous carcinoma or lymphoma was also reactive with B72.3 MAb. Our findings show that, in the colon, expression of TAG-72 antigen occurs during the process of epithelial cell transformation but is also regulated by factors unrelated to the process of carcinogenesis.