Previous work has demonstrated that E2F proteins regulate the expression of various genes encoding proteins essential for DNA replication and cell-cycle progression. E2F1 in particular is required for the initial entry to the cell cycle from a quiescent state and is required for the activation of other E2F genes. Other work has demonstrated a role for the Myc transcription factor in the activation of a large number of genes associated with cell growth, including E2F genes. We now show that Myc is required to allow the interaction of the E2F1 protein with the E2F gene promoters. As such, Myc thus provides a link between the development of a growth-competent state during the initial stage of G(1) and the activation of genes essential for DNA replication at G(1)/S.