Despite extensive efforts the aetiology of Crohn's disease hasyet to be established. Studies have concentrated on possible infectious or immunological causes, but have not provided a clear explanation of the pathogenesis of this disease. Many infectious agents such as bacteria, viruses, mycoplasma, and mycobacteria have been considered as possibly causing Crohn's disease. 1-3 So far none of the infectious agents have fulfilled Koch's postulates or beenconsistently confirmed as a causative agent of this disease. Possible immunological abnormalities have also been studied. 4 Numerous investigators have looked for either primary immunological abnormalities5 or abnormalities of immune response. 6 Again, none of these efforts have consistently identified immunological abnormalities as the cause of Crohn's disease. 78 Prostanoid metabolism has recently received extensive scrutiny in the search for the aetiology of Crohn's disease. Numerous investigators have been able to show increased PGE2 concentrations in inflamed colonic mucosa9'or colonic lumenal contents from patients with Crohn's disease.'1 Increased elaboration of other prostanoids9 1213 and leucotrienes"has also been reported in patients with Crohn's disease. The consensus of opinion is that changes in prostanoid metabolism in Crohn's disease are probably secondary to the inflammatory process itself and not an underlying aetio-logical factor. 14

While the aetiology and pathogenesis of Crohn's disease is complex, I propose that increased intestinal permeability through abnormal tight junctions could play a role. I am not proposing that increased intestinal permeability is the only aetiological factor in the development of Crohn's disease; rather, I am proposing thatincreased intestinal permeability could allow the penetration of antigenic or infectious agents into the intestinal wall and thus start the process which in susceptible individuals culminates in Crohn's disease. The proposal that increased intestinal permeability could be important is not new.'5 Recent new clinical and experimental evidence,'" 2'however, is sufficient to suggestserious consideration of this proposal as a working hypothesis.