OBJECTIVE: Patients with extensive and long-standing ulcerative colitis have an increased risk of developing colorectal cancer and sub-epithelial fibrosis. The polypeptide transforming growth factor alpha (TGF-alpha) has mitogenic effects and it is believed that local overproduction may result in tumour formation and fibrosis. DESIGN: In the present study, we correlated the presence of TGF-alpha in ulcerative colitis with the degree of inflammation and with dysplasia. METHODS: Sixty two patients were investigated, 46 with ulcerative colitis (16 with active inflammation and 20 in remission, 10 with dysplasia of the colon), and 16 controls with normal colonoscopy and without a history of colitis. There were no overlaps between the subgroups. Tissue sections from colonic biopsies were examined and TGF-alpha was detected by immunohistochemistry. TGF-alpha-containing cells were characterized by double-staining with antibodies to eosinophil cationic protein (ECP). An antibody (EG2) recognizing eosinophils with an activated phenotype was also used. RESULTS: The median number of TGF-alpha-containing cells in the mucosa was 24 per mm2 (inter-quartile range 10-51) in controls, 186 per mm2 (73-245) in ulcerative colitis with active inflammation, 76 per mm2 (52-198) in remission, and 130 per mm2 (66-203) in areas of dysplasia. Double-staining for TGF-alpha and ECP revealed that most of the TGF-alpha-containing cells were eosinophils, and most had an activated phenotype as judged by staining with EG2. CONCLUSIONS: The presence of TGF-alpha-containing cells in colonic mucosa is increased both in active inflammation and during remission in ulcerative colitis. Dysplasia is not associated with any significant increase in TGF-alpha-containing cells. The majority of TGF-alpha-containing cells are eosinophils with an activated phenotype. TGF-alpha released from these cells could be important for the development of complications seen in ulcerative colitis, such as cancer and fibrosis.