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Aim: To determine the differences in efficacy between therapy using IFN-beta and ribavirin, and using IFN-alpha and ribavirin., Methods: We studied the effect of combination therapy consisting of IFN-beta and ribavirin on mouse hepatitis virus (MHV) infection in mice., Results: Combination treatment of ribavirin and IFN-alpha was more effective than IFN-alpha mono-treatment in the MHV-mouse system, and combination treatment with ribavirin and IFN-beta was more effective than IFN-beta mono-treatment in the MHV-mouse system. Furthermore, administering IFN-beta once or twice one day before combination treatment using ribavirin and IFN-alpha was more effective than administering IFN-alpha once or twice one day before the combination treatment using ribavirin and IFN-alpha., Conclusion: These data indicate that this MHV-infection system is a good animal model to assess anti-HCV activity for therapy using IFN and ribavirin, and suggest that administering IFN-beta before the start of combination therapy with ribavirin and IFN-alpha promotes the therapeutic effects of combination treatment with ribavirin and IFN-alpha ?in chronic hepatitis C patients.