Interferon zeta (IFN-zeta)/limitin has been regarded as a novel type I IFN by the Nomenclature Committee of the International Society for Interferon and Cytokine Research. IFN-zeta/limitin, which has some sequence homology with IFN-alpha and IFN-beta, has a globular structure with 5 alpha helices and 4 loops and recognizes IFN-alpha/beta receptor. Although it displays antiviral, immunomodulatory, and antitumor effects, IFN-zeta/limitin has much less lymphomyelosuppressive activity than IFN-alpha. Unique interactions between IFN-zeta/limitin and the receptor probably led to the narrow range of signals and biological activities. A human homologue of IFN-zeta/limitin may be clinically more effective than IFN-alpha and IFN-beta because it has fewer adverse effects. Moreover, further analysis of the structure-function relationship may establish an engineered cytokine with the useful features of IFN-zeta/limitin.