The differential reactivity of four mouse monoclonal antibodies (AbCB, AbHT29-36, AbM2, and AbS12) and Dolichos biflorus lectin with A1 and A2 erythrocytes was analyzed. Only AbS12 and D. biflorus lectin were able to preferentially agglutinate A1 erythrocytes. AbS12 is known to react only with short chain, unbranched structures (such as Aa-2 and Ab-2 glycolipids) and not with longer chains or with type 3 and type 4 structures. D. biflorus was shown to have a similar specificity by lectin staining of glycolipids separated by thin-layer chromatography. Analysis of the binding of radiolabeled AbCB and AbS12 to A1 and A2 erythrocytes by Scatchard analysis showed that, whereas the former antibody recognizes high-affinity sites on both A1 and A2 cells, AbS12 reacts with high-affinity sites only on A1 cells. Because A1 and A2 erythrocytes have a similar complement of short chain type 2 glycolipids, although in different amounts, it is suggested that AbS12 and D. biflorus lectin differentiate between the two cell types on the basis of quantitative, nonstructural features. This is in contrast to AbTH1, which reacts with a repetitive A epitope (type 3 A chain) and distinguishes between A1 and A2 cells based on the preferential expression of type 3 A chains in A1 erythrocytes. Thus, two views of A1/A2, i.e., qualitative vs quantitative are correct, depending on the properties of the reagent being used to distinguish between the two cell types.