Here we present data indicating that influenza A viruses are not only capable of suppressing production of the IFNb gene but also inhibit action of this antiviral cytokine on cells. This occurs by viral induction of a cellular protein, the suppressor of cytokine signaling (SOCS)-3, a potent endogenous inhibitor of IFN signaling. This is a novel mechanism by which influenza viruses inhibit the antiviral response of the host and paves the path to efficient virus replication. This may be especially relevant for influenza viruses that induce high cytokine responses (cytokine burst), such as highly pathogenic avian influenza viruses of the H5N1 subtype. Induction of SOCS-3 expression would allow efficient replication despite high IFN and cytokine levels.