The aim of this study was to investigate whether immunoregulatory invariant NK T cells are deficient in Crohn's disease or ulcerative colitis. Blood was collected for flow cytometry from 106 Crohn's disease, 91 ulcerative colitis, and 155 control subjects. Invariant NK T cells were assessed by Valpha24 and (alpha-galactosylceramide/CD1d tetramer markers. Intracellular cytokine was measured after in vitro anti-CD3 antibody stimulation. Valpha24+ T cells were quantified in ileocolonic biopsies as mRNA by real-time PCR and by immunofluorescence. Circulating invariant NK T cells were 5.3% of the control levels in Crohn's (P < 0.001) and 7.9% of the control levels in ulcerative colitis (P < 0.001). Interleukin-4 production was impaired in Crohn's disease and ulcerative colitis. Intestinal Valpha24 mRNA expression was 7% in Crohn's disease (P < 0.05) and 9% in ulcerative colitis (P < 0.05). Intestinal Valpha24+ T cells were 23% in Crohn's disease but not reduced in ulcerative colitis. We conclude that invariant NK T cells are deficient in Crohn's disease and in ulcerative colitis.