We are studying the detailed receptor requirements of a group of animal viruses known to utilize sialyloligosaccharides of glycoproteins or glycolipids as host cell receptor determinants. These include influenza viruses, paramyxoviruses, polyoma virus and encephalomyocarditis virus. The interaction of these viruses with erythrocytes or cells in culture can be assessed by hemagglutination or infectivity, respectively. In either case, removal of cell surface sialic acids with neuraminidase prevents attachment of the virus. Sialyloligosaccharides of defined sequence can be introduced on the surface of the asialo-cells by reaction with purified sialyltransferases. By examining the ability of the sialyloligosaccharides elaborated by different sialyltransferases to restore viral hemagglutination to erythrocytes or viral infection to cultured cells, the receptor specificity of the virus can be defined. It is clear that these viruses can exhibit strict and varied specificities for sialyloligosaccharide receptors. Potential biological roles for viral receptor specificities in host selection will be explored.