In D. melanogaster, CycE and E2F1 are critical proteins in endocycle control. It is known that both of these proteins are required for endocycling and that cycE mRNA and protein oscillate in endoreduplicating tissues (ERT’s). The mechanism of endocycle regulation by E2F1 through CycE, however, has not been elucidated. Here, I implicate E2F1 protein oscillation in the fluctuation of two of its specific target genes, cycE and rnr2, which is then responsible for the G-S transition ofDrosophila ERT’s. The results also suggest that E2F1 control of S phase initiation within the endocycling cell is dependent on nutritional inputs.