A comprehensive, systematic and integrated investigation will be undertaken of the blood group antigens present on erythrocytes, other cellular elements of blood and tissues, and in body fluids or secretions of man and animals, and their defining antibodies of several human systems. The major approach focuses on the fundamental immunologic characteristics of human blood group isoantigens and antibodies in attempts to determine the structural basis for immunologic specificity and to relate their physicochemical properties with serologic specificity. Heavy emphasis will be placed on ABO and related blood group systems, such as Lewis and I, and P. Experiments are planned to differentiate the immune anti-A antibodies of ABO hemolytic disease of the newborn; to study the comparative serology of A antigens and anti-A antibodies using red cells, secretions and immunization of animals to discern subspecificities; to examine the isohemolysins of human serum, especially with the technique of hemolysis in agar gel; to investigate serologically and immunogenically A substances secreted in the saliva of group A persons, especially the group A variants; to characterize and explain the structural and biosynthetic basis for variants of the blood group A antigen; to analyze the Bombay phenotype (Oh) immunologically and to ascertain its structural basis; to determine the relationship of sheep anti-H antibodies to sheep blood groups; to detect and characterize human blood group antigens present on tissues; to extract human blood group antigens of both glycoprotein and glycolipid classes from erythrocytes and tissues, and examine these for precise specificity and chemical nature; to examine the basic properties of blood group specific lectins and to broaden their utility in blood group research; and to characterize the I blood group system antigens and other cold reacting antibodies.