Revised Manuscript Received March 10, 1994s abstract: The immunoglobulin E-binding protein, eBP (also known as CBP35, Mac-2, L-34, and L-29), is a/3-galactoside-binding protein of approximately 30 kDa and a member of the animal lectin family termed S-type or S-Lac. Multiple biological activities have been attributed to this lectin such as mediation of IgE binding to the surface of Langerhans cells and activation of mast cells throughbinding to the high affinity IgE receptor. In order to better understand the cell-binding activity and the proposed role for eBP as a biological response modifier, we have studiedthe specificity of binding of the radioiodinated eBP to a series of lipid-linked, structurally defined oligosaccharide sequences of the lacto/neolactofamily. Theresults show that the minimum lipid-linked oligosaccharides that can support eBP binding are pentasaccharides of the lacto/neolacto series and that the lectin binds more strongly to oligosaccharides of this family that bear the blood group A, B, or B-like determinants than to those bearing blood groupH. This preferential binding of eBP is also manifest with wholecells, as erythrocytes of blood groups A and B are more strongly bound by eBP than those of blood group O. Blood group Lea and Le* sequences are not bound by the lectin. The present results in the context of the earlier observations on the specificity and biologicalactivity of eBP raise the possibility that, in vivo, its degree of cell association and thresholds for activation of various cells of the immune system, and by inference allergic predispositions, may be influenced by blood group status and other polymorphic carbohydrate antigen systems based on lacto/neolacto backbones.