Orally administered autoantigens suppress autoimmunity in animal models, including experimental allergic encephalomyelitis, collagen and adjuvant-induced arthritis, uveitis, and diabetes in the non-obese diabetic mouse. Low doses of oral antigen induce antigen-specific regulatory T-cells in the gut, which act by releasing inhibitory cytokines such as transforming growth factor-β, interleukin-4, and interleukin-10 at the target organ. Thus, one can suppress inflammation at a target organ by orally administering an antigen derived from the site of inflammation, even if it is not the target of the autoimmune response. Initial human trials of orally administered antigen have shown positive findings in patients with multiple sclerosis and rheumatoid arthritis. A double-blind, placebo-controlled, phase III multi-center trial of oral myelin in 515 relapsing-remitting multiple sclerosis patients is in progress, as are phase II clinical trials investigating the oral administration of type II collagen in rheumatoid arthritis, S-antigen in uveitis, and insulin in type I diabetes.