Rheumatoid arthritis (RA) is a chronic, prevalent, and disabling autoimmune disease that occurs when inflammation damages joints. Recent advances in neuroscience and immunology have mapped neural circuits that regulate the onset and resolution of inflammation. In one circuit, termed “the inflammatory reflex,” action potentials transmitted in the vagus nerve inhibit the production of tumor necrosis factor (TNF), an inflammatory molecule that is a major therapeutic target in RA. Although studied in animal models of arthritis and other inflammatory diseases, whether electrical stimulation of the vagus nerve can inhibit TNF production in humans has remained unknown. The positive mechanistic results reported here extend the preclinical data to the clinic and reveal that vagus nerve stimulation inhibits TNF and attenuates disease severity in RA patients.