Transforming growth factor-alpha (TGF-alpha) and related peptides have been implicated in a wide range of biological activities, including cell growth, differentiation and acid inhibition. This chapter reviews the roles of TGF-alpha in the stomach, the insights gained into the action of the TGF-alpha family of growth factors from the study of polarized epithelial cells and the confirmation of events mediated by the epidermal growth factor receptor (EGFR) by the study of mice in which the EGFR has been disrupted by homologous recombination.