The present invention relates generally to the generation and characterization of neutralizing anti-IFN- alpha monoclonal antibodies with broad reactivity against various IFN- alpha subtypes. The invention further relates to the use of such anti-IFN- alpha antibodies in the diagnosis and treatment of disorders associated with increased expression of IFN- alpha , in particular, autoimmune disorders such as insulin-dependent diabetes mellitus (IDDM) and systemic lupus erythematosus.