Accumulation of histo-blood group antigens such as Lewis b, Lewis Y and H increases tumor cell motility and tumorigenesis. Alpha1,2-fucosylation is a key step in the synthesis of these antigens. Two alpha1,2-fucosyltransferases, expressed in colorectal carcinomas, have been characterized (FUT1 and FUT2 in humans, FTA and FTB in rats). To define the relative contribution of each of these enzymes in tumor cell behavior, we have used an anti-sense transfection approach in rat colon carcinoma PROb cells, which synthesize mRNA encoding for both enzymes. We have previously reported that anti-sense transfection of a cDNA fragment of the FTB enzyme decreased H antigenic cell-surface levels and concomitantly decreased tumorigenicity. H antigens, detected by antibodies specific for H type 1, 3 or 4, were detected only on a splice variant of CD44 containing the product of exon v6. We now report the anti-sense transfection of an FTA cDNA fragment into PROb cells, which resulted in decreased enzymatic activity on a type 2 precursor and decreased cell-surface H type 2 antigen exclusively. Compared to controls, FTA anti-sense-transfected cells were significantly more tumorigenic in syngeneic animals but not in immunodeficient SCID mice. The UEA-I lectin, specific for H type 2, revealed that these structures were present on the CD44v6 variant and on an uncharacterized 80-kDa glycoprotein. Our results indicate that FTA and FTB fucosylate distinct glycan chains in the same cell, leading to opposite effects, under control of the immune system.