An enzyme-linked immunosorbent assay (ELISA) for studying erythrocyte A, B and H epitope specific exoglycosidases is described. Human blood type B erythrocyte membranes and Coffea canephora alpha-D-galactosidase were used as a model. Membrane coated microtiter wells were incubated with exoglycosidase, probed with IgM monoclonal antibody, and then with anti-murine mu chain specific alkaline phosphatase conjugate. The assay is useful for studying exoglycosidase modification of the A, B and H epitopes on human erythrocyte membranes as well as in screening prokaryotic and eukaryotic extracts for blood group active enzymes. Furthermore, this technique has the advantage of simplicity, sensitivity, and objectivity of data interpretation.