This chapter summarizes the experimental evidence bearing on the nature of virus-erythrocyte reactions characteristic of several taxonomic groups.. Such evidence is culled from (1) the study of conditions necessary for hemagglutination; (2) the examination of specific factors affecting either the cell or the virion to enhance, alter, or abolish the reaction; and (3) the direct physicochemical analysis of cells, viruses, and “receptor analogs.” The hemadsorption phenomenon also provides evidence for virus-erythrocyte interactions, which is based on the attachment of erythrocytes to infected cells in culture having hemagglutinin at their surfaces. This phenomenon reflects the interaction between erythrocytes and viral envelope components. The major virus groups that react with erythrocytes include myxoviruses, paramyxoviruses, pseudomyxoviruses, adenoviruses, arboviruses, reoviruses, enteroviruses, and miscellaneous hemagglutinating viruse (rubella virus, coronaviruses, rhabdoviruses, and oncogenic viruses). The agglutination of erythrocytes by the direct action of viral particles was first described in connection with myxoviruses. This led directly to the discovery of viral neuraminidase—a property unique to myxoviruses and paramyxoviruses. A number of viruses unrelated to myxoviruses have since been shown to agglutinate erythrocytes of various species. The visible result of viral hemagglutination is the “pattern” formed at the bottom of a test tube or well plate by lattices of red cells lightly conjoined by viral hemagglutinin. Hemagglutination serves as a useful direct means of titering intact viral particles or hemagglutinating subunits.