Human erythrocyte membrane proteins express antigens which serve as markers for erythroid differentiation as well as targets for human blood group alloantibodies. We have produced and characterized a new panel of five monoclonal antibodies to erythrocyte membrane proteins. Three monoclonal antibodies (E3, E4, E5) were specific for erythrocyte glycophorins. One antibody (E3) identified the sialoglycoprotein alpha and beta homologous regions proximal to the plasma membrane, a second antibody (E4) was specific for sialoglycoprotein alpha, while a third (E5) was a sialoglycoprotein-beta-specific antibody. Two antibodies (E6 and TE10) to the 65,000-dalton chymotrypsin cleavage product of band 3 were also produced. These antibodies constitute a new panel of probes for investigation of normal erythroid differentiation, erythroleukemia, and the expression of normal and anomalous blood group antigens.