Epidermal growth factor (EGF) binds to the specific membrane receptor and subsequently activates the signal transduction pathway through intrinsic tyrosine kinase activity. To elucidate the mechanism in which structural alteration of the EGF may affect functional properties including its receptor binding ability, site-directed mutagenesis has been employed. The functional significance of structural characteristics of the EGF receptor has been studied also by mutant receptor constructs in the transfected cells. Recent progress on the studies of the EGF and EGF receptor interaction are reviewed.