Immunohistologic techniques were used to study the expression of colorectal carcinoma-associated antigens in colonic polyps and to compare this with expression in the normal colonic epithelium. Forty-nine polyps were studied using monoclonal antibodies to 16 different blood group and differentiation antigens and carcinoembryonic antigen epitopes. With the Lewis(a) antigen and the two epitopes of CEA recognized by 3D6 and COL-4 expression in polyp tissue was the same as that in the normal colon. Five types of alteration of antigen expression in polyps were seen. The blood group antigens A, B, and Lewis(b), which are expressed only on the right side of the normal adult colon, were detected in both neoplastic and nonneoplastic polyps from the distal colon. The Lewis(x) antigen and the antigen epitopes detected by the antibodies COL-12, CA19-9, ME491, and GA73.3 showed an increased frequency of expression in all types of polyps in comparison with the normal colonic epithelium, while H-type 2, ND4, and the antigen epitope detected by CO29.11 showed a slightly decreased frequency of expression in polyp tissue. The X-like antigen which was expressed in only 7% of normal colon specimens showed increased frequency of expression in polyp tissue with significantly greater expression in neoplastic than hyperplastic lesions (P = 0.003). The TAG-72 antigen was detected only in adenomas with severe dysplasia (P = 0.01), correlating well with premalignant histology. These findings have helped us clarify the variation of antigen expression in colonic polyps and allowed us to define which antigens are worthy of further investigation as markers of possible malignant transformation.