Reciprocal hemagglutination inhibition titrations were carried out with viruses and antisera of eight field strains of the A3 subtype of influenza A, covering the period from 1968 to 1975. The earlier strains (1968 through 1972) showed asymmetric cross-reactions, with antisera exhibiting more cross-reactions with antecedent strains than with subsequent ones. The later strains, although all were asymmetrically cross-reactive with earlier strains, tended to exhibit distant and variable cross-reactions with each other. The numbers and average affinities of antibody molecules capable of taking part in cross-reactions were calculated from equilibrium filtration experiments. It was found that all the antibody molecules in sera raised against the late strains could combine with earlier viruses, but with reduced affinity. Conversely, only a subset of the antibody molecules in sera raised against early strains could combine with later viruses. The results are discussed in the light of different theories concerning the nature and number of antigenic determinants on the hemagglutinin molecule. They support the existence of a single antigenic area to which all antibody molecules are directed, with differing affinities, rather than the existence of both "common" and "specific" determinants. Thermodynamic measurements on the homologous antigen-antibody reactions indicated that combination was mostly entropy driven. This suggested hydrophobic interaction as the mechanism of combination, i.e., that the complementary regions of antigen and antibody were made up largely or entirely of amino acids with hydrophobic side chains. There was no statistical difference in the magnitude of the entropy term (i.e., the average firmness of binding) among the different virus strains.