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BACKGROUND/AIMS: The study of graft versus host disease of the intestine has significant clinical relevance and may also be a model for other immune mediated intestinal diseases. There presently is no simple non-invasive test that can be used to evaluate graft versus host disease induced intestinal injury in humans or animal models. This study tested the hypothesis that graft versus host disease leads to an increase in host bowel permeability as assessed by the relative urinary excretion of orally administered lactulose and rhamnose. METHODS: The urinary excretion ratio of orally administered lactulose and rhamnose was determined daily for two weeks in (Lewis x Brown-Norway) F1 rats with graft versus host disease caused by either the transplantation of parental (Lewis) small bowel or the intraperitoneal injection of parental (Lewis) splenic lymphocytes. RESULTS: Significant twofold to fourfold increases in the lactulose to rhamnose ratio were seen in both small bowel transplant and splenic lymphocyte transfer animals suffering from graft versus host disease during the second postoperative week. This effect occurred sooner in small bowel transplant than in splenic lymphocyte transfer animals (postoperative day 7 versus 11, respectively). The signs of graft versus host disease, including splenomegaly and altered intestinal mucosal architecture, as well as the increased lactulose to rhamnose ratio were significantly attenuated in small bowel transplant animals treated with cyclosporine A (10 mg/kg/day). CONCLUSIONS: Graft versus host disease is associated with an increase in the lactulose to rhamnose clearance ratio reflecting an increase in host bowel permeability. This increase, along with the signs of systemic graft versus host disease, can be significantly ameliorated by cyclosporine A. The lactulose to rhamnose clearance ratio is a non-invasive technique that can be used to assess the intestinal effects of graft versus host disease and the associated increase in intestinal permeability.