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Orally administered [51Cr]EDTA was used to measure intestinal permeability in subjects with infectious diarrhea and in those without gastrointestinal complaints. [51Cr]EDTA was given to 87 subjects: 63 controls (32 normal controls, and 31 disease controls), and 24 patients with infectious diarrhea. Approximately 100 microCi of [51Cr]EDTA was given orally after an overnight fast. Urine was collected for the following 24 hr. Intestinal permeability to [51Cr]EDTA in both normal volunteers and in patients with a variety of diseases not associated with intestinal injury was low and results were in a relatively narrow range. Mean 24-hr urinary excretion of [51Cr]EDTA, calculated as a percent of the administered dose, in controls was 1.6% (0.2-3.5%). Patients with infectious diarrhea associated with invasive pathogens and/or intestinal inflammation had increased excretion of [51Cr]EDTA (mean 6.1%, P < 0.0001), with elevated excretions in 75%. These results demonstrate that intestinal infections must be considered as possible causes for increased intestinal permeability as assessed by the [51Cr]EDTA test.