Publisher Summary When it became clear that a number of plant viruses are crystallizable macromolecules composed of ribonucleic acid and protein, it was possible to attribute to a particular sort of macromolecule the striking biological property of autoreproduction. It could be imagined that this extraordinary property was a consequence of the particular arrangement of the atoms forming the nucleoprotein. Since the nucleoprotein nature of genes had been suspected for some time, it became only natural to consider that the activities of genes, too, were natural consequences of a nucleo-protein structure. In the past, a very high degree of autonomy has been assigned to both genes and viruses. Thus, the very fact of a particle being composed of nucleoprotein could be considered to result in a high degree of autonomy in the cell. Two very important modifications are taking place in our thinking about autoreproducing particles. In the first place, it is becoming more evident that the autonomy of any element of a living cell is only very relative. This is true of the nuclear gene whose function and perhaps even structure may be modified by the conditions prevailing in the cell as a whole. It is equally true for viruses, for one is beginning to recognize the real restrictions of the autonomy of viruses. One such restriction is clearly demonstrated by host specificity; a virus may penetrate into a cell but fail to reproduce itself, even though the cell is synthesizing the nucleotides and amino acids presumably necessary for the reproduction of the virus. Another such restriction can be seen in the recent demonstrations of host-induced modifications of viruses. The purpose of this chapter is to summarize, in general, the present knowledge of transformation and transforming factors, and then to enter in detail into the evidence indicating the complex nature of the contribution of the cell to the reproduction of nucleic acid introduced into the cell in the form of a transforming agent.