All human Adenoviruses (Ads) transform rodent cells in culture and induce tumours in immunodeficient animals. However, only oncogenic serotypes (e.g. Ad 12) induce tumour growth in immunocompetent rodents. The transforming and oncogenic potential of Ads is located in the early viral genes Ad-E1A and Ad-E1B. One prerequisite for tumour induction in immunocompetent rodents is the ability of the Ad 12-E1A oncoproteins to interfere with components of the host’s cell immunity to avoid elimination of transformed cells by the host’s immune system. Due to this interference Ad12-E1A-transformed cells are less sensitive to NK-cell killing compared to cells transformed by non oncogenic Ads. Moreover, these cells show a reduced expression of major histocompatibility complex (MHC) class I molecules on their cell surface, thus preventing the elimination through cytototic T lymphocytes (CTLs). Suppression of MHC class I cell surface expression occurs at several levels among which down-regulation of MHC class I promoters is of particular importance. In this review we will summarize our current knowledge about the interference of Adl2-ElA gene products with the host’s immune system and will discuss those mechanisms that are responsible for Ad12-E1A-mediated repression of MHC class I gene expression.