General aspects of nucleic acid uptake by mammalian cells have been the subject of several reviews during the last few years (PAGANO, 1970; BHARGAVA and SHANMUGAM, 1971; DUBES, 1971; RYSER, 1967). These reviews covered methods used for the infection of cells by viral nucleic acids as well as interaction of mammalian cells with non-viral nucleic acids. This article is restricted to a discussion of experiments with poliovirus RNA and focuses special attention on the steps following the uptake of RNA into a cell, aspects that were not discussed in earlier review articles. The fate of input RNA once inside the cell is determined by the host cell but experimental conditions can be chosen to favor the survival of input RNA and the induction of a virus growth cycle by interfering with host-cell metabolism through events that, in the case of infection with intact virus, might be controlled by viral proteins.