Aim: Crohn's disease (CD) is a chronic mucosal inflammation that affects the intestinal barrier function, for example, by altering the intestinal permeability. This pilot clinical study investigated the impact of oral human immunoglobulin (OHIG) treatment on permeability characteristics in children with active luminal Crohn's disease. Methods: The study was performed at the Department of Paediatrics, Norrkoping Hospital, Sweden. Intestinal permeability was studied in three boys aged 13, 15 and 18 years with active CD, before and after a six-week treatment programme with OHIG, using different-sized polyethylene glycols as the test molecules. Three age-and sex-matched children with active CD treated with exclusive enteral nutrition (EEN) were also studied. Results: OHIG and EEN resulted in virtually similar reductions in the signs and symptoms of mucosal inflammation. However, OHIG, unlike EEN, appeared to normalise mucosal transfer leading to a normalisation of the maximum permeation of the small PEG molecules, as well as less restrictions of the larger PEG molecules. Conclusion: Our study found that OHIG appeared to normalise the mucosal barrier. This suggests that it could offer a new additional and versatile treatment for paediatric CD patients, with a minimal risk of adverse effects.