The development of monoclonal antibodies (MAbs) to tumour-associated antigens has allowed the successful radioimmunolocalization of a variety of tumours and has provided a basis for targeted therapy. In patients with colorectal cancer, antibodies to CEA have been the most widely used for imaging, but their role in targeted therapy may be inhibited by their reaction with normal tissues and with circulating CEA. Epithelial-membrane antigen (EMA) is expressed by most epithelial tumours, including colorectal cancers, and antibodies to EMA may provide a satisfactory alternative. We therefore compared two high-affinity MAbs, one to CEA (C46) and one to EMA (ICR2), in tissues obtained from 31 patients with cancer (18 primary colonic, 6 nodal metastases and 7 liver metastases), 14 patients with adenomatous polyps and 17 with normal colon. The indirect immunoperoxidase staining reaction was used and the results classified as either positive or negative. A heterogeneous pattern of staining was found for both antibodies. ICR2, the anti-EMA, reacted with slightly fewer colonic cancers than C46, the anti-CEA antibody (83% vs. 100%) and a similar number of metastases. Most noticeable was the minimal reaction of anti-EMA with normal colon (12% vs. 71%) and benign polyps (7% vs. 79%) in comparison to anti-CEA. This would suggest a possible role for ICR2 in the radioimmunolocalization and targeting of colorectal cancer.