Type I interferons (IFNs) such as IFN-a are important mediators during antiviral responses. In normal individuals, plasmacytoid dendritic cells (DCs) are a major source of IFN-a in vivo. For about 2 decades, it has been known that elevated levels of type I IFNs are found in the serum of patients with systemic lupus erythematosus (SLE), a prototypic autoimmune disease. Moreover, treatment of various diseases with IFN-a often leads to antinuclear autoantibody production and frank autoimmunity, including SLE. The role that IFN-a has in SLE pathophysiology is just beginning to be explored.