Mucosal ulceration in the gastrointestinal tract leads to the development of a novel cell lineage which locally secretes growth factors such as trefoil peptides and epidermal growth factor (EGF). Gastric mucosal ulceration causes an increase of EGF receptor density and a profound decrease of somatostatin receptor density in the mucosal ulcer margin and scar. These changes in growth factors and their receptors cause a strong increase of cell proliferation in the ulcer margin. In experimental ulcer models, EGF and basic fibroblast growth factor (bFGF) promote ulcer healing by increasing epithelial cell proliferation and angiogenesis, respectively. Indomethacin delays ulcer healing by decreasing epithelial cell proliferation, inhibition of angiogenesis, and inhibition of remodelling of the granulation tissue in the ulcer base. Indomethacin interferes with EGF binding and proliferative response of gastric cultured KATO III cells. In addition, bFGF cannot reverse indomethacin-induced deleterious effects on experimental gastric ulcer healing. In summary, growth factors play an important role in promoting wound healing in benign gastrointestinal diseases.