Different cell types in the body of higher animals undergo terminal differentiation. In such a process, cells acquire specialized functions and irreversibly lose their ability to divide, therefore entering the postmitotic state. Terminally differentiated cells do not proliferate in response to growth factors or following the expression of activated, retroviral oncogenes. In this paper we demonstrate that adenovirus infection is an efficient and convenient means to induce terminally differentiated cells to reenter the cell cycle. These findings constitute a first step toward defining the molecular determinants of the irreversible withdrawal from the cell cycle of terminally differentiated cells. They may also open the way to therapeutic applications.