Bacterial co-infections are a major complication in influenza virus-induced disease both in humans and animals. Either of the pathogens may induce a host response that affects the infection by the other pathogen. A unique feature in the co-infection by swine influenza viruses (SIV) and Streptococcus suis (S. suis) serotype 2 is the direct interaction between the two pathogens. It is mediated by the hemagglutinin of SIV that recognizes the ?2,6-linked sialic acid present in the capsular polysaccharide of S. suis. In the present study, this interaction was demonstrated for SIV of both H1N1 and H3N2 subtype as well as for human influenza viruses that recognize ?2,6-linked sialic acid. Binding of SIV to S. suis resulted in co-sedimentation of virus with bacteria during low speed centrifugation. Viruses bound to bacteria retained infectivity but induced only tiny plaques compared to control virus. Infection of porcine tracheal cells by SIV facilitated adherence of S. suis which was evident by co-staining of bacterial and viral antigen. Sialic acid-dependent binding of S. suis was detectable already after incubation for 30 min. On the other hand, bacterial co-infection had a negative effect on the replication of SIV as indicated by lower virus titers in the supernatant and a delay in the kinetics of virus release.