SV40 DNA replication has been studied extensively as a model for eukaryotic DNA replication. The initiation of SV40 DNA replication depends on certain cellular enzymes and on a multifunctional viral phosphoprotein, T antigen, whose activity is controlled positively and negatively by its phosphorylation state. Several cellular protein kinases and phosphatases that act on T antigen have now been identified. The recent elucidation of the step in initiation that is sensitive to T antigen's phosphorylation state raises the question of whether initiation of cellular DNA replication may utilize a similar regulatory mechanism.