Reovirus induces IFN, and reovirus is sensitive to the antiviral actions of IFN. The characteristics of the IFN-inducing capacity of reovirus, and the antiviral actions of IFN exerted against reovirus, are dependent upon the specific combination of reovirus strain, host cell line, and IFN type. Responses, both IFN induction and IFN action, differ quantitatively if not qualitatively and are dependent upon the virus, cell, and IFN combination. Stable natural dsRNA, identified as the form of nucleic acid that constitutes the reovirus genome, is centrally involved in the function of at least three IFN-induced enzymes. Protein phosphorylation by PKR, RNA editing by the ADAR adenosine deaminase, and RNA degradation by the 2',5'-oligoA pathway all involve dsRNA either as an effector or as a substrate. Considerable evidence implicates PKR as a particularly important contributor to the IFN-induced antiviral state displayed at the level of the single virus-infected cell, where the translation of viral mRNA is often observed to be inhibited following treatment with IFN-alpha/beta. In the whole animal infected with reovirus, elevated cellular immune responses mediated by enhanced expression of MHC class I and class II antigens induced by IFN-alpha/beta or IFN-gamma may contribute significantly to the overall antiviral response.