Background: A large family of Moroccan immigrants was investigated. In this family the father developed Crohn's disease (CD) after moving from Morocco to Belgium and successively 4 of his 8 children subsequently developed CD. There was no previous history of familial CD.Methods: The family was interviewed at their home and an elaborated questionnaire was completed. The food and sanitation characteristics of the family were investigated. Moreover, serological markers were tested in all family members, including ASCA, ASCAg, ALCA, ACCA, Omp, and ANCA, using enzyme-linked immunosorbent assay and indirect immunofluorescence. Genetic variants in CARD15, TLR4, NOD1, CARD8, and DLG5 associated with CD were tested as well. The complete medical history of all patients was reviewed.Results: There were no known genetic variants associated with CD in this family. None of the serological antibodies could discriminate between patients and unaffected family members, although the antibody titers were higher in diseased family members as compared with the healthy family members.Conclusion: The occurrence of 5 new cases of CD within 1 Moroccan family after immigration to Belgium cannot be explained by the known genetic susceptibility factors, and thus suggests a major environmental factor probably not related to sanitation in childhood.(Inflamm Bowel Dis 2007).