During Drosophila oogenesis nurse cells become polyploid, enabling them to provide the developing oocyte with vast amounts of maternal messages and products. The nurse cells then die by apoptosis. In nurse cells, as in many other polyploid or polytene tissues, replication is differentially controlled and the heterochromatin is underreplicated. The nurse cell chromosomes also undergo developmentally induced morphological changes from being polytene, with tightly associated sister chromatids, to polyploid, with dispersed sister chromatids. We used female-sterile dE2F1 and dDP mutants to assess the role of the E2F cell cycle regulator in oogenesis and the relative contributions of transcriptional activation versus repression during nurse cell development. We report here that E2F1 transcriptional activity in nurse cells is essential for the robust synthesis of S-phase transcripts that are deposited into the oocyte. dE2F1 and dDP are needed to limit the replication of heterochromatin in nurse cells. In dE2F1 mutants the nurse cell chromosomes do not properly undergo the transition from polyteny to polyploidy. We also find that dDP and dE2F1 are needed for nurse cell apoptosis, implicating transcriptional activation of E2F target genes in this process.