A panel of monoclonal antibodies produced against surface membrane components of the human colon tumor cell line Caco-2 was found to define oncofetal crypt cell antigens (CCA) expressed by fetal intestinal cells, adult small intestinal crypt cells, and human and rat colonic adenocarcinomas. The epitopes recognized by these antibodies have been identified as O-linked oligosaccharide chains associated with specific glycoproteins in cultured intestinal cells and in colon tumors in vivo. Analysis of a large group of normal and diseased human intestinal specimens has demonstrated a marked heterogeneity in CCA expression which correlated with the degree of organization of the tumor cells in the tissue, suggesting that the CCA represent useful histological and clinical markers for colon cancer.