Analyses of the reactions of monoclonal anti-D with Rh D variant red cells have shown that there are at least 24 different epitopes of the Rh D antigen. Similar studies Of Rh E variant red cells with monoclonal anti-E indicate that there are at least 4 epitopes of the Rh E antigen. The relation of these serologically defined epitopes to the structure of the Rh proteins is reviewed. Most epitopes are discontinuous, with critical residues present in different loops of the proteins.