BACKGROUND: Intestinal mucositis is an important cause of cancer treatment-related morbidity and mortality, carrying a serious economic burden. Currently, objective parameters are lacking that would enable the monitoring of gut damage in routine clinical practice, thus hindering the development of clinical studies designed to investigate potential new strategies aimed at reducing or preventing this side effect. The authors investigated the characteristics of serum citrulline concentration compared with sugar permeability tests with respect to its use as a marker for cancer treatment-induced small bowel injury. METHODS: In this prospective study, 10 patients with hematologic malignancies who were receiving myeloablative therapy had gut toxicity assessed with sugar permeability tests. Serum citrulline concentrations also were determined using archival serum samples. The association between both parameters and their respective characteristics were analyzed and compared with data from the literature. RESULTS: Sensitivity and specificity were better for the citrulline assay compared with sugar permeability tests. Maximum gut damage assessed with the citrulline assay was observed 1-2 weeks earlier compared with the sugar permeability test. Similarly, citrulline indicated recovery of gut damage at 3 weeks after transplantation, whereas most sugar permeability tests remained abnormal. CONCLUSIONS: The simplicity of the method, the low costs, and the lack of drawbacks to the method make the citrulline assay the first choice for measuring and monitoring treatment-related gut damage and provides an objective parameter for cancer treatment-related gut toxicity.