Sendai virus (SeV) renders cells unresponsive to interferon (IFN)-K K. To identify viral factors involved in this process, we examined whether recombinant SeVs, which could not express V protein, subsets of C proteins (C, CP P, Y1 and Y2) or any of four C proteins, retained the capability of impeding IFN-K K-mediated responses. Among these viruses, only the 4C knockout virus completely lost the ability to suppress the induction of IFN-K K-stimulated gene products and the subsequent establishment of an anti-viral state. These findings reveal crucial roles of the SeV C proteins in blocking IFN-K K-mediated responses.z 1999 Federation of European Biochemical Societies.