Blood group ABH determinants have been characterized as being carried by eight classes of carbohydrate chains (see Progress Report and Appendix Table I). Combinations of determinants and carrier molecules result in extensive variation in blood group structures, and each combination of a determinant with its carrier can be recognized by a specific monoclonal antibody which does not cross react with the same ABH determinant bound to a different carrier. Our previous studies also indicate the following possibilities for oncofetal expression of blood group antigens: (1) In human teratocarcinoma, and perhaps in human embryo, the pattern of carrier-determinant combinations is quite different from that in normal adult tissue, i.e., a blood group determinant with a globoseries core predominates over that with a lacto-series core structure. A globoseries blood group antigen may also be present in some human cancer. (2) In addition, human cancer displays two types of significant differences in blood group determinants themselves: (a) the appearance of incompatible blood group determinants foreign to the host, and (b) the accumulation of precursor structures due to incomplete synthesis of blood group determinants. This application is to study: (1) the relationship between ABH determinants and their carrier carbohydrate chains, their distribution patterns, and the specificity of the combinations, (2) the globo-series blood group antigens in normal adult and fetal tissues and in various cancer tissues, (3) differentiation of the specific enzymes that make ABH determinants with type 1 chain, type 2 chain, and extended globo-series structure, (4) incompatible blood group antigens in human cancer, with particular emphasis on A-like antigen in tumors of blood group O/or B individuals, and (5) preliminary studies on isolation of genes that define incompatible transferases.