Orally administered (51)Cr-labelled ethylenediaminetetraacetic acid ((51)CrEDTA) has been used to evaluate intestinal permeability in inflammatory bowel disease, especially Crohn's disease. However, information about colonic permeability in ulcerative colitis (UC) is relatively scarce. The aim of this study was to investigate the urinary excretion of orally administered (51)CrEDTA, its relation to disease activity and its response to medical therapy in patients with UC. Forty-three patients with UC and 19 controls were examined. Disease activity was evaluated by endoscopy. In 19 patients with active UC, the (51)CrEDTA permeability test was repeated after medical therapy. (51)CrEDTA (95 microCi; 26 MBq) was given orally after an overnight fast and urine was collected over a 24 h period. The first urine samples were taken 5 h and the second 24 h after the oral administration of (51)CrEDTA. Urine samples were counted in a gamma counter. In controls, the median 5 h and 24 h excretions were 0.10% and 0.93%, respectively. Patients with UC showed significantly increased urine (51)CrEDTA excretion at both time intervals (5 h: 2.41%, P<0.0002; 24 h: 6.72%, P<0.0001). There was also a significant correlation between intestinal permeability and disease activity (5 h: r=0.45, P=0.0025; 24 h: r=0.51 P=0.0006). After medical therapy, (51)CrEDTA urinary excretion was significantly decreased (pre-treatment UC: 7.87%; post-treatment UC: 2.50%; P<0.0002). Briefly, the (51)CrEDTA test reflected colonic permeability in UC and might be useful as an indicator of disease severity. Moreover, this study suggested that, in patients with UC, medical therapy not only leads to the recovery of acute inflammation but also restores mucosal barrier integrity and function.