Non-steroidal anti-inflammatory drugs induce damage throughout the entire gastrointestinal tract. Administration of site-specific permeability probes is a non-invasive technique for assessing the functional integrity of the gastrointestinal mucosa. A systematic search tor NSAID-induced permeability studies using MEDLINE and EMBASE, and an analysis of the literature on NSAID-induced gastrointestinal permeability, were carried out. The advantages and disadvantages of the various probes and study protocols are discussed. Identification of the underlying mechanisms of regulatory control of the epithelial tight junction is still needed. A greater appreciation of the pharmacokinetics and distribution of NSAIDs, coupled with gastrointestinal permeability studies, may help delineate the pathogenesis of NSAID-induced gastrointestinal toxicity. Non-invasive tests of gastric, intestinal and colonic permeability have shown promise in both basic research and in clinical practice. While such tests could not replace endoscopy, they may represent clinically useful techniques for identifying patients who would benefit from endoscopy, to assess the response to treatment, and perhaps to predict the clinical course of disease.