A patient with presumed rheumatoid arthritis based on clinical and serological evidence was subjected by her physician to interferon-gamma (IFN-gamma) therapy and developed a life threatening multiorgan flare of systemic lupus erythematosus (SLE). Pulse cyclophosphamide therapy in conjunction with plasmapheresis led to complete remission. Retrospective analysis of serum drawn before IFN-gamma was started revealed high DNA binding capacity. Thus, similar to observations in lupus-prone animals, IFN-gamma may have induced an exacerbation of preexisting SLE.