The TFA is a tumor-associated, blood-group-related glycosidic precursor structure [Gal(beta 1-3)GalNAc]. Its expression in carcinomas is accompanied by a decrease of natural TFA antibodies in serum. The relationship between the ABO(H)-blood-group phenotype and natural anti-TFA immune response in patients with gastric cancer was studied. The level of TFA agglutinins in the sera of patients with gastric cancer and of healthy controls was examined by the hemagglutination of neuraminidase-treated blood-group-O donor erythrocytes. Individuals were classified as weak or strong TFA responders. They were also classified by ABO(H)-blood-group status, age, cancer stage, tumor morphology and level of isohemagglutinins. The proportion of weak TFA responders (WR) in cancer patients was 33, 50, 50 and 20% (for O, A, B and AB blood groups respectively), as compared with 11.7, 14.5, 13.9 and 26.1% for blood-group-related controls. The difference between cancer patients and controls was significant for all blood groups except group AB. Further analysis showed age-dependence in blood-group-O and -B controls, with a high level of WR in the older group. Blood-group-A cancer patients had the greatest and uniform suppression of the level of TFA agglutinins, irrespective of age, cancer stage or tumor morphology, and lower levels of anti-B isohemagglutinins.