Current efforts to understand regulation of replication and cell growth often focus on initiation of DNA replication at an origin sequence. It is most likely, although not yet proven in eukaryotes, that the ultimate step in the regulation of the G to S transition in the cell cycle is the priming of DNA synthesis at an origin. The study of this process in eukaryotic cells has progressed slowly, and most of the attention has centered upon the replication of virus DNAs in infected cells. Although this provides practical advantages, it may be limited in its generality since viral DNAs replicate many times throughout the course of an infection, disregarding the constraints normally placed upon chromosome replication. Nevertheless, an understanding of the mechanism of initiation in eukaryotes is necessary, and the availability of virus origins dictates that they be studied first.