Research in Drosophila melanogaster has made significant contributions to our understanding of both the mechanistic basis of immunity and the ecological and evolutionary factors contributing to phenotypic variation in immune system function. However, research into the molecular mechanisms of immunity has tended to neglect factors contributing to phenotypic variation in immune function, while research focused on the factors contributing to phenotypic variation has been compromised by an incomplete understanding of its genetic basis. Phenotypic changes may arise in responses to environmental changes (phenotypic plasticity) or due to changes in the genotype. The main goal of the proposed research is to examine changes in gene expression contributing to environmental and genetic improvements in the antimicrobial immune response in Drosophila melanogaster. The availability of the complete Drosophila genome, along with micro-chip gene arrays, allowing genome-wide analysis of gene expression, will provide an unprecedented examination of the genetic basis of improvements in immune function and the potential costs associated with these improvements. Results will contribute to understanding the mechanistic basis of insect immune function, the evolution of inducible defense, the maintenance of susceptibility to infectious disease, and to the link between the genotype and the phenotype. ? ?