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Restless legs syndrome (RLS) is a common disorder for which agents that enhance dopaminergic activity, including dopamine agonists and levodopa, are the treatment of choice. However, long-term use of dopaminergic drugs can cause unwanted effects such as rebound, tolerance, and augmentation. Bupropion, an inhibitor of dopamine and noradrenalin reuptake, is an antidepressant that modulates dopaminergic systems. The authors report that a low dose of bupropion rapidly and completely ameliorated RLS symptoms in 3 depressed patients within a few days of the initiation of treatment. To their knowledge, this is the first report to show that bupropion may be an effective alternative for treating RLS. Consequently, bupropion may be useful for the treatment of patients with both depression and RLS.