Evidence suggests that CD4(+) CD25(+) regulatory T cells play a crucial role in the suppression of intestinal inflammation. However, their role in the suppression of inflammatory bowel disease has not yet been addressed. We examined the proportion of regulatory T cells in inflammatory bowel disease. First, we isolated CD4(+) CD45RO(+) CD25(+) T cells from the peripheral blood of healthy persons and showed that these cells suppressed T cell proliferation profoundly and expressed FoxP3 abundantly, revealing that they are regulatory cells. Then the proportion of CD45RO(+) CD25(+) in peripheral blood CD4(+) T cells was analyzed in patients and healthy controls by flow cytometry. CD4(+) CD45RO(+) CD25(+) T cell frequency was significantly lower in active ulcerative colitis than in the control and inactive ulcerative colitis. CD4(+) CD45RO(+) CD25(+) T cell frequency was inversely correlated with the clinical and endoscopic severity of ulcerative colitis. These results suggest that a deficiency of regulatory T cells is associated with the progression of ulcerative colitis.