The human intestine contains two populations of anatomically distinct T cells, intraepithelial lymphocytes and lamina propria lymphocytes (LPLs), both of which preferentially use the TCR-alpha beta. Recent studies of TCR alpha- and beta-chain usage by intestinal intraepithelial lymphocytes, which are predominantly CD8+ T cells, have demonstrated that these cells are oligoclonal in normal intestine. This report examined the TCR beta-chains expressed by purified CD4+ and CD8+ T cells from normal colonic lamina propria and from the intestinal mucosa of patients with active ulcerative colitis (UC). The selective expansion of CD8+ T cell clones, and to a lesser extent CD4+ T cell clones, was observed among both normal LPLs and mucosal T cells in UC. These expanded LPL clones from normal donors were all distinct, but the mucosal T cells isolated from five of nine patients with UC contained CD8+ T cells expressing related V beta 3-J beta 1.6 TCRs. These observations provide evidence for an Ag-specific mucosal T cell response in UC. Further studies will be required to identify this Ag and address whether the T cell response to it plays a primary role in initiating the disease or is secondary to the inflammatory response.