This paper addresses seven questions with respect to the transfer, integration, amplification and genetic stability of recombinant DNA in mammalian genomes. Most of these questions were raised with those issues in mind which are frequently discussed in the context of the manufacture of biologicals of therapeutic value on the basis of recombinant cell lines. For the most part, a high degree of ignorance has to be acknowledged and only very limited fragments of information are available. The reason for this ignorance is, as will become clear from this article, the sheer size and complexity of the mammalian genome and the inadequacy of presently available tools to unravel this complexity.