Although patients with systemic lupus erythematosus (SLE) are known to have elevated circulating levels of leptin, the role of leptin in the pathogenesis of the disease has been unclear. Now, in new research, genetic deficiency of leptin is shown to protect mice against the development of pristane-induced SLE manifestations (autoantibody production and renal disease). Conversely, in a mouse model of spontaneous SLE, leptin administration accelerated the disease. The finding of a promotional role for leptin in SLE raises the possibility that leptin-targeted therapies could be used to treat the disease.