Intestinal epithelial barrier function and Crohn’s disease are intimately related. An impaired barrier in association with active inflammation leads to increased exposure of the mucosal innate and acquired immune system to proinflammatory molecules. This has been implicated as a major driving force for mucosal inflammation. In active disease, macromolecules can permeate the barrier at an increased rate via, for example, breaks in the integrity of the epithelium (ulceration, erosions, or nests of apoptotic cells) 1 via increased pinocytotic uptake of luminal proteins, 2 3 and via increased proportion of M cells in the terminal ileum. 4 Impaired barrier function may precede the clinical development of the disease and might represent a marker of increased susceptibility to Crohn’s disease. This notion derives from observations made in several centres using different techniques that paracellular permeability is abnormal in 10–20% of first degree relatives of patients with Crohn’s disease. 5–10 That this reflects exposure to an environmental factor is supported by the observations from three studies that increased intestinal permeability is also found in 13–36% of spouses of patients with Crohn’s disease. 8 9 11 Tumour necrosis factor o (TNF-o) and Crohn’s disease are intimately related. Mucosal levels and inflammatory cell production of TNF-o are elevated. Therapy with monoclonal antibodies to TNF-o, such as infliximab, leads to a rapid reduction in inflammation and healing in many patients, and remission can be maintained with ongoing therapy. 12–14 The spectacular effect of infliximab has been attributed not only to its ability to mop up TNF-o but also to induction of apoptosis in activated T cells. 15