The aims of this work were to define more fully the disease spectrum of patients with EcAbs, investigate the immunological expression of ECs in order to detect any characteristics of EcAb positive or other enteropathies, Crohn's or other colitides & histologically normal controls & set up a colonic culture system to investigate the effects of immunomodulators on EC immunological expression. There were 3 categories of patients with EcAb: i. Classical autoimmune enteropathy with high EcAb titres, severe enteropathy, ± colitis, ICAM-1 on ECs (unique to this disease entity) & aberrant crypt EC HLA-DR (also seen in other enteropathies. ii. Sub-group of food sensitive enteropathy (FSE) with moderate EcAb titres, reduced villous & patchy crypt EC HLA-DR (also seen in FSE without EcAb) with response to hypoallergenic diet. iii. low titres of EcAb in association with a wide variety of gastrointestinal disorders, presumably as an epiphenomenon. In all enteropathies & colitides studied aberrant EC HLA-DR with higher incidence of cytokine expression by ECs than lamina propria cells was seen. Colonic adhesion molecule expression varied in both colitides and controls indicating lability. Colonic culture demonstrated greatest secretion of IL-1 & other proinflammatory cytokines in Crohn's colitis & 'in-vitro' tissue damage associated with TNF. In conclusion autoimmune disease of the intestinal EC has been described. The EC plays an active role in the mucosal immune response in chronic inflammatory diarrhoeal disorders. The EC should be considered part of the intestinal immune system.