The T-antigen (Thomsen-Friedenreich antigen) is a well-characterized tumor-associated glycoprotein that is immunologically reactive in humans. In order to demonstrate the presence of T-antigens in colorectal tissue, benign and malignant tissue from 46 patients with colorectal cancer were examined by means of an immunoperoxidase method. Peanut agglutinin and a polyclonal immune rabbit antiserum were used to demonstrate T-antigens on 72% of formalin-fixed malignant specimens and on more than 92% of frozen malignant specimens. Both ligands bound to the cell membrane and secreted mucus, but only the rabbit serum showed routine staining of the cytoplasm. The T-antigen distribution was heterogeneous without relation to degree of differentiation. Transitional mucosa adjacent to malignant tissue showed a strong anti-T binding to secreted mucus. Slightly morphologically altered crypts remote from the carcinoma expressed T-antigens. Unexpectedly, both ligands bound to nerve cells of the enteric ganglia. These contain gangliosides with immunodominant oligosaccharides identical with those on the T-antigen. Therefore, cross-reactions might have occurred between the gangliosides and the used ligands. The T-antigens now seem to be present in various widespread cancers, and they probably occur early in malignant transformation.