Damage to the mucosal barrier may be assessed, non-invasively by use of sugar probes, which permeate through the transcellular or paracellular (tight junction) routes. A standardised test, with analysis of a five hour urine collection has proved useful in studying the sequelae of non-steroid anti-inflammatory drug (NSAID) administration, untreated coeliac disease, and enteric infections. Choice of probe molecule is crucial and lactulose/l-rhamnose seem to be satisfactory, in contrast with polyethylene glycol. Significant correlations have been seen between permeability and plasma IgA concentrates in nephropathy, and between permeability and the passage of neutrophil chemotactic agents. The increased permeability associated with NSAID treatment may relate to the adverse effects of NSAIDs on enterocyte mitochondrial morphology and metabolism. These two factors may predispose the mucosa to permeation of bacterial chemoattractant molecules that elaborate a local inflammatory response. A similar mechanism may operate in patients with untreated Crohn's disease, who show abnormally high permeability. Remission induced by treatment with elemental diets coincides with a reduction in permeability. The period to relapse correlated with the inability of patients to maintain low permeability to sugar probes. These results suggest a mechanism for the benefits of elemental enteral nutrients in the treatment of Crohn's disease.