Diagnosis of intestinal transplant rejection depends on clinical assessment, endoscopy and most importantly, histology of intestinal biopsies. Plasma citrulline levels (P-Cit) reflect functional enterocyte mass in nontransplant patients and have been evaluated in two small series after transplant. This study was designed to determine the sensitivity and specificity of P-Cit as diagnostic tool for allograft injury, especially to distinguish between viral enteritis and rejection. We prospectively collected 403 P-Cit samples within 24 h of intestinal biopsy in 49 patients. P-Cit levels were correlated with the mucosal damage and histopathological diagnoses. P-Cit levels in bowels with significant mucosal damage (i.e. moderate or severe rejection, viral enteritis, PTLD, ischemia reperfusion injury, allergic enteritis) were significantly lower than in intestines with no or mild injury (i.e. indeterminate or mild rejection, nonspecific enteritis): 22.9 +/- 15.4 versus 38 +/- 23.2 nmol/mL (p < 0.0001). Sensitivity and specificity of the test were 80% and 58.1% for rejection, and 56.5% and 66% for viral enteritis, thereby unable to distinguish between both entities. In conclusion, P-Cit reflects the extent of mucosal injury regardless of the etiology, but does not seem to be a predictive marker for rejection or viral enteritis, as its values may decline only when diffuse mucosal damage has occurred.