In the present study the authors investigated the T-cell response to different enterobacteria or Helicobacter pylori and tested the hypothesis that the frequency of bacteria-specific T cells is increased in the intestine of patients with active inflammatory bowel disease (IBD), i.e. Crohn's disease (CD) and ulcerative colitis (UC). The analysis of a large panel of T-cell clones (Tc) (n = 888) from peripheral blood, non-inflamed and inflamed intestine from IBD patients and control individuals shows that both peripheral blood and intestinal T-cell clones were selectively stimulated by either Salmonella typhimurium, Yersinia enterocolitica 03, Escherichia coli or Helicobacter pylori sonicates, that only < 3% of all bacteria-reactive Tc were crossreactive and that proliferation to bacterial sonicates was inhibited by anti-MHC class II antibody. In addition, bacteria-specific Tc from IBD patients were more frequently isolated from inflamed intestine than from peripheral blood (P = 0.0039) or non-inflamed intestine. These data, from a large number of T-cell clones, are the first systematic analysis describing the response of individual T cells towards different bacterial species (ssp.). They show that T cells with specificity for distinct antigens or superantigens that are characteristic for a defined bacteria ssp. are present in normal, and increased in inflamed, IBD-intestine. These bacteria-specific Tc may play a role in IBD pathogenesis.