Interferons (IFNs) are a group of cytokines which exhibit pleitropic activities that play major roles in both innate and adaptive immunity. Type I IFNs consist of multiple IFN-alpha (IFN-α) genes and at least one IFN-beta (IFN-β) gene in most vertebrates, and a few other family members such as limitin in the mouse. There are 14 IFN-alpha subtypes in the mouse which share at least 75% identity in protein sequence. In the human, IFN-alpha is used to treat viral diseases and cancer and is studied in mouse models of these diseases. Recent evidence has suggested that IFN-alpha may play a role in development of certain autoimmune diseases and that treatment with IFN-alpha is useful for other autoimmune diseases.