Interferon (IFN)-induced antiviral activity in cells forms an important early line of defense against viral pathogens. IFN-induced mediators are well documented in mammals, with one of the best-characterized antiviral proteins being Mx. In chickens, many alleles of Mx have been described, but functionally only the polymorphism at a site encoding residue 631 in the protein determines differential antiviral activity against vesicular stomatitis virus and influenza virus in transfection experiments. The role of chicken Mx has not been assessed with regard to infectious bursal disease virus (IBDV), an important pathogen of chickens. To examine the role of chicken IFNα and the Mx631 single-nucleotide polymorphism against IBDV, chicken embryo fibroblast cultures (CEF) that differed in Mx genotype (antivirally positive Mx Asn631 or antivirally negative Mx Ser631) were treated with IFNα and viral yield was assessed following infection with D78 vaccine-strain IBDV. IFNα was shown to have strong antiviral activity in this system in terms of reduced virus yield. Furthermore, the reduction in viral yield did not differ significantly among Mx genotypes, indicating that Mx Asn631 is not a pivotal determinant of resistance to this strain of IBDV in CEF.