Drosophila immunity and embryogenesis appear to be linked by an evolutionarily ancient signalling pathway, which includes the Rel-domain transcription factors Dif and dorsal, respectively, as well as a common inhibitor, cactus. Previous genetic screens have centered on maternal mutants that disrupt the dorsal pathway. In an effort to identify additional components that influence Rel-domain gene function we have conducted a search for immunodeficiency mutants in Drosophila. One such mutant, which maps near the Black cells (Bc) gene, causes a severe impairment of the normal immune response, including attenuated induction of several immunity genes. Survival assays indicate a positive correlation between the induction of these genes, particularly diptericin, and resistance to bacterial infection. These studies are consistent with the notion that insect anti-microbial peptides work synergistically by binding distinct targets within infecting pathogens. Evidence is also presented that non-specific acquired immunity results from the persistence of bacterial metabolites long after primary infection. We discuss the potential usefulness of this study with regard to the identification of conserved components of Rel signalling pathways.