A method for the modification of the oligosaccharide moiety of even small amounts of purified glycoproteins by enzymatic glycosylation and deglycosylation is described. The method includes noncovalent immobilization of the glycoproteins onto the polystyrene surface of the wells of microtiter plates used as reaction tubes, deglycosylation or glycosylation by incubation either with exoglycosidases or endoglycosidases or with glycosyltransferases, and the characterization of the modified glycan structures by probing them with lectins. Placental transferrin receptor employed as a model glycoprotein was modified in amounts of as little as (100 \mathrm{ng}) removing sialic acid residues, hybrid-type glycans or all types of (N)-glycans with neuraminidase, endo- (\beta) - (N)-acetylglucosaminidase H or peptide- (N^{4})-(acetyl- (\beta)-glucosaminyl) asparagine amidase. Asialotransferrin receptor was (\alpha-2,6)-sialylated with (\alpha-2,6)-sialyltransferase from rat liver, but could not be (\alpha-2,3)-sialylated with (\alpha-2,3-) sialyltransferase from porcine liver. Changes in the structure and in the relative amount of the oligosaccharides could be monitored semiquantitatively with high sensitivity by the binding of digoxigenin-labeled lectins and anti-digoxigenin Fab fragments. The method is easy to use, does not require immobilization of the enzymes employed, offers simple separation of the enzymes and the product, and leaves the protein intact for further studies. 1993 Academic Press, Inc.