An ELISA assay is described for measuring the binding of influenza virus A-X31 to alpha-sialoside groups that are linked to biotin-labeled polyacrylamides. The efficacy of these polymers in inhibiting the adhesion of influenza virus to erythrocytes (as measured by a hemagglutination assay) was shown to be directly related to the binding affinity of the polymers for the viral surface : the differences in inhibitory efficacy among the polymeric inhibitors and monomeric alpha-methyl sialoside, among fractions of a polymeric, polyvalent inhibitor with narrow molecular weight ranges, and among polymeric inhibitors prepared by copolymerization or modification of a preformed polymer chain, all correlated with differences in the affinity of the inhibitors for the surface of the virus, The polymeric inhibitors studied had affinities for the viral surface that ranged between 10(3) and > 10(6) greater than alpha-methyl sialoside, on the basis of total sialic acid groups in solution, The role of steric stabilization in the mechanism by which these polymers inhibit hemagglutination was investigated, The ability of the polymeric, polyvalent inhibitors to inhibit the binding of a polyclonal antibody to the viral surface suggests that steric stabilization may also be an important effect in this system.