The immune system in the intestine must respond rapidly to invading pathogens without mounting sustained effector cell responses to the indigenous commensal bacteria. Results from this laboratory using the T cell transfer model of colitis suggest that specialized populations of regulatory T cells control the immune response in the intestine. Regulatory T (Tr) cell activity is enriched within the naturally arising CD4(+) CD25(+) Tr subset that has been shown to prevent a number of inflammatory diseases. CD4(+) CD25(+) Tr cells control intestinal inflammation induced by both innate and adaptive immune responses via IL-10- and TGF-beta-dependent mechanisms. Recent results have shown that CD4(+) CD25(+) Tr cells can cure established colitis, suggesting their utility for the treatment of inflammatory bowel disease.