The antigenic determinants of blood groups A, B and O erythrocytes can be altered by the action of two types of enzymes: transferases and glycosidases. Only the latter, however, will remove the antigen’s immunodominant sugars which are N-acetylgalactosamine in the case of A and D-galactose for B. Their removal results in the formation of group O cells since neither of these sugars are part of the antigenic determinant of these cells. Glycosidases are being used in an attempt to produce enzymatically converted group O cells of transfusable quality. It has been shown that by using an α-galactosidase from green coffee beans, group B cells can be transformed to O under conditions which do not adversely affect the treated cell’s membrane integrity and metabolic viability. Preclinical studies using small quantities of such cells have demonstrated that they survive normally in the circulation of A and O recipients whose immune systems would not tolerate untreated cells and that converted cells are not immunogenic under these conditions. Further studies are planned with larger amounts of converted cells. Treatment of A erythrocytes with an α-N-acetylgalactosaminidase isolated from chicken liver has also begun. Successful enzymatic production of group O cells of transfusable quality from A and B erythrocytes could have many beneficial effects upon the practice of transfusion medicine.