BACKGROUND AND GOALS: In the clinical management of celiac disease, new noninvasive tools for evaluation of intestinal damage are needed for diagnosis and for follow-up of diet effects. Fatty acid binding proteins (FABP) are potentially useful for this purpose as these are small cytosolic proteins present in enterocytes and sensitive markers for intestinal mucosal damage. First, the distribution and microscopic localization of FABP in the healthy human intestine was examined. Second, levels of circulating FABP were measured in patients with celiac disease before and after introducing a gluten-free diet (GFD) and in healthy controls. STUDY: The distribution and microscopic localization of FABP in normal human intestinal tissue was assessed using surgical intestinal specimens of 39 patients. Circulating levels of intestinal (I)-FABP and liver (L)-FABP were determined in 26 healthy volunteers and 13 patients with biopsy proven celiac disease. Ten of these patients were reevaluated within 1 year after starting GFD. RESULTS: I-FABP and L-FABP are predominantly present in the small intestine, mainly the jejunum. Moreover, FABP are expressed in cells on the upper part of the villi, the initial site of destruction in celiac disease. Circulating levels of FABP are significantly elevated in untreated patients with biopsy proven celiac disease compared with healthy controls (I-FABP: 784.7 pg/mL vs. 172.7 pg/mL, P<0.001; L-FABP: 48.4 ng/mL vs. 10.4 ng/mL, P<0.001). In response to GFD, these concentrations normalize. CONCLUSIONS: Results of this pilot study strongly suggest that FABP can be used as a noninvasive method for assessment of intestinal damage in celiac disease. Besides an additional role in the diagnosis of celiac disease, FABP potentially enable noninvasive monitoring of the GFD effects.