Monoclonal antibodies have proven to be invaluable reagents for the characterization and purification of human interferons (IFN). Hybridoma lines secreting monospecific antibodies against human IFN-α and IFN-β have been isolated, and these antibodies have shown no cross-reactivity between the two interferons1–4. Murine interferons, when analysed by polyacrylamide gel electrophoresis, have two major migration patterns, one in the 28,000–35,000 (28–35 K) molecular weight (Mr) region and the second in the 22 K region5–8. Based on some homology of the N-terminal amino acid sequence with human interferons, the 28 K and 35 K species are classified as mouse IFN-β and the 22 K species as mouse IFN-α9. Minor species have also been described but their relationship to IFN-α and IFN-β is unknown10,11. We have now established a stable hybridoma line secreting rat antibodies to mouse virus-induced interferon. The monoclonal antibodies are of the IgG class, with binding activity to all the different Mr specied, as demonstrated in an enzyme-linked immunosorbent assay (ELISA) and by affinity chromatography. In addition, the antiviral activity of all the Mr species was neutralized by the antibody but the neutralizing activity was much weaker than the binding activity. This indicates the presence of a common antigenic site for all mouse α and β interferon species.