A panel of 7 mouse monoclonal antibodies and the lectin from Ulex europeus, detecting blood-group-related antigens of the ABH and Lewis systems, have been used to define the distribution of these antigenic structures within the human gastrointestinal tract, and to characterize their expression and modulation in colorectal carcinomas. The reagents employed detect the following blood-group specificities: A (all variants), B, H (type 2), Lewisa, Lewisb, X (Lewisx), Y (Lewisy) and type 1 precursor chain. Immunohistochemical studies demonstrate that these antigens are differentially expressed in various cell types and developmental stages of the human gastrointestinal tract. ABH expression undergoes developmental modulation in the human colorectal tract from positive to negative during embryogenesis, and is lost in adult cells. Colorectal tumors exhibit neosynthesis of ABH specificities that appear in tumor cells, and accumulation of the precursor antigens. They also show increased expression of Lewis antigens, especially Y determinant, which has a restricted pattern of distribution in normal tissues and is not found in normal colonic mucosa. Enhancement of the Lewis antigens is observed in all colorectal tumors analyzed, regardless of blood-group type and secretory status of the individuals studied. Tumor modulation of these antigens may be related to activation of suppressed genes and enhancement of fucosyltransferases.