The expression of the cellular gene coding for the epidermal growth factor (EGF) receptor (EGF-R) was assayed in the presence of hepatitis B virus (HBV) gene expression under different experimental conditions in human hepatoma-derived cells. First, transfection experiments of the well-differentiated HepG2 human hepatoma cell line using different expression vectors of the HBV X-region demonstrated that the X-gene product is capable of inducing EGF-R gene overexpression; in addition, by using a stable in vitro expression system for HBV, it was shown that EGF-R gene expression in these cells is greater than in the uninfected parent cells, and that this results in a three-fold increase in ¹²⁵I-EGF binding. Finally, a CAT-expression assay was performed, indicating that regulatory regions of the EGF-R-gene are target sequences for X-protein trans-activation.