The C and V proteins of the measles virus (MV) have been shown to block the signaling of type I and II interferon (IFN-α/β and IFN-γ). The relative contribution of the C and V proteins to the inhibition of IFN signaling and the extent to which this activity differs in attenuated or wild-type strains of MV remains undefined. This study presents a comparison of the IFN-antagonist activities of C and V proteins from four attenuated and two wild-type strains of MV. The V proteins were more potent inhibitors of IFN-inducible reporter gene expression than the C proteins, and this effect was unrelated to whether the protein originated from an attenuated or wild-type strain. The results also demonstrated the importance of the tyrosine at position 110 in the inhibition of IFN-α/β and IFN-γ signaling by the V protein, and identified a non-recombinant MV expressing a V protein that was impaired due to a mutation at this residue.