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To evaluate whether fecal calprotectin (FC) and fecal lactoferrin (FL) can be used as noninvasive markers in children and young people (4–17 years) with active inflammatory bowel disease (IBD).Stool samples were collected from 3 groups of children: those with active IBD, control individuals with other gastrointestinal (GI) diseases (GI control) and control individuals with no GI disease (non-GI control). The number of patients for the FC assay was as follows: IBD = 26, GI control = 30, non-GI control = 25. The number of patients for the FL assay was as follows: IBD = 24, GI control = 26, non-GI = 24. FC and FL were measured by use of enzyme-linked immunoassays.The median concentrations of FC and FL in isolation, and their interaction, were significantly higher in the IBD group than in the GI and non-GI control groups (P < 0.001). Although the area under the curve, sensitivity, and specificity for FC, FL, and FC × FL interaction were significantly better than chance, FL consistently had the lowest area under the curve, and FC × FL consistently had the highest area under the curve.FC and FL are both significantly elevated in children with IBD, and the interaction of these 2 biomarkers may produce a better initial diagnostic test compared with their use in isolation.