In disease states of the small intestine--for example, gluten-sensitive enteropathy--there is an increased permeability to large molecules. This increased permeability extends to polar molecules of intermediate size such as disaccharides, whereas small polar molecules are malabsorbed. A recently-developed oral test, based on the simultaneous administration of two test substances, cellobiose (a disaccharide) and mannitol (a small polar molecule) has been used to investigate permeability in a variety of gastrointestinal diseases, the result of the test being expressed as the ratio (cellobiose/mannitol) of the five hour urinary recoveries of the two probe molecules. Results for patients with pancreatic insufficiency, intestinal bacterial overgrowth, primary hypolactasia, ileocolic or colonic Crohn's disease, and ulcerative colitis were comparable with those in normal controls, whereas in 23 out of 24 untreated coeliacs, and five out of eight patients with Crohn's disease involving the more proximal small bowel, the cellobiose/mannitol ratio was clearly abnormal. A study of its application as a screening procedure for coeliac disease showed that the test was both sensitive and accurate, with fewer false-positive and false-negative results than other recognised screening tests--namely, the xylose test, reticulin antibodies, and blood folate estimations.