Autoimmunity appears to be a key factor in Crohn's disease as it develops in a genetically susceptible host if the immunological tolerance towards bacterial antigens within the gastrointestinal tract is abrogated. The resulting excessive immunological activity leads to a chronic sometimes transmural inflammatory process within the bowel wall. However, several lines of evidence are compatible with an immunodeficiency preceding these processes: humoral or cellular immune defects can predispose to inflammatory bowel disease. An increased bacterial adherence at the intestinal mucosa, which is possibly attributable to impaired expression of defensins was observed in Crohn's disease. Furthermore, the 3020insC mutation of the NOD2/CARD15 gene which is associated with Crohn's disease results in impaired cytokine transcription. Lastly, therapeutic approaches such as the use of antibiotic therapy or granulocyte macrophage colony stimulating factor are in line with the concept of an immunodeficiency being a crucial element in Crohn's disease.