AbstractLife-history theory posits that investment into reproduction might occur at the expense of investment into somatic maintenance, including immune function. If so, reduced or curtailed reproductive effort might be expected to increase immunity. In support of this notion, work in Caenorhabditis elegans has shown that worms lacking a germline exhibit improved immunity, but whether the antagonistic relation between germline proliferation and immunity also holds for other organisms is less well understood. Here, we report that transgenic ablation of germ cells in late development or early adulthood in Drosophila melanogaster causes elevated baseline expression and increased induction of Toll and Imd immune genes upon bacterial infection, as compared to fertile flies with an intact germline. We also identify immune genes whose expression after infection differs between fertile and germline-less flies in a manner that is conditional on their mating status. We conclude that germline activity strongly impedes the expression and inducibility of immune genes and that this physiological trade-off might be evolutionarily conserved.