Objective Citrulline is a nonprotein amino acid synthesized in the small intestine. The aim of this study is to explore plasma citrulline levels in children with celiac disease (CD) and monitor the time-related changes of these levels after initiation of a gluten-free diet (GFD). Methods Fasting-plasma citrulline levels were determined by high-performance liquid chromatography in (i) 23 patients with CD before the institution of GFD, (ii) 20 patients with CD under treatment for more than 2 years responsive to a GFD, (iii) 10 children with gastrointestinal symptoms and normal small bowel biopsy, and (iv) 20 healthy controls. In group A, citrulline levels were also measured after 1, 3, 6, and 12 months on a GFD. Results Mean plasma citrulline levels were lower in untreated patients with CD (24.5 +/- 4.9) than in patients on a GFD (31.2 +/- 6.7 mu mol/l, P < 0.001), patients with gastrointestinal symptoms and normal intestinal mucosa (30.3 +/- 4.7 mu mol/l, P < 0.01), and healthy controls (32.4 +/- 7.5 mu mol/l, P < 0.001). In untreated patients with CD, an inverse correlation was observed between citrulline concentrations and the severity of villous atrophy (r=-0.67, P < 0.01). After 1 month on a GFD, patients had significantly higher levels than before diet (P < 0.05) and after 3 months on diet, levels were similar to those observed in the healthy controls. Conclusions Plasma citrulline levels are lower in celiacs reflecting small bowel involvement in this disease. After a short period on GFD, citrulline levels increased rapidly, indicating that citrulline is a sensitive marker of the positive effect of GFD on intestinal repair. Eur J Gastroenterol Hepatol 23: 245-249 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.