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Dipeptidyl peptidase IV (DPP IV/CD26) is involved in the degradation of proline-rich proteins such as gliadin and in modulation of the immune response. The aim of this study was to examine the possible causal connection between DPP IV enzyme activities and celiac disease (CD) in children.Intestinal mucosal biopsy specimens were obtained from 97 patients. The patients were divided into 3 groups: patients with active CD (n = 38), patients with malabsorption syndrome (MS) of other causes (n = 37), and control patients (n = 22). In addition, blood samples were collected from 48 patients with active CD and 50 control patients without gastrointestinal diseases. DPP IV enzyme activity was measured in the intestinal mucosal biopsy specimens and in the serum samples.DPP IV activity in the small intestine correlated inversely with the grade of mucosal damage in the CD (r = −0.92, P < 0.001) and MS groups (r = −0.90, P < 0.001). Intestinal DPP IV activity was statistically significantly lower in the CD and MS groups than in the control group (P < 0.001). By contrast, serum DPP IV activity was not significantly different between the CD and control groups.Our results suggest that the decrease in intestinal DPP IV activity is not specific to CD because it correlates with the level of mucosal damage in both patients with CD and those with MS. In addition, it seems that serum DPP IV activity cannot be used as a specific noninvasive diagnostic or prognostic marker of CD.