Daphnia and their parasites have long been a model for the study of host-parasite interactions, in particular for research on genetic variation for susceptibility. These studies have almost invariably been confined to the analysis of whole organism phenotypes, for example how parasite-induced host mortality varies depending on host genetic background. This work now stands to be revolutionized by the sequencing of the Daphnia genome and the development of post-genomic technologies. With these genomic resources in place, it is now possible to identify the immune system genes that underlie resistance variation among hosts, and then determine how parasites drive the evolution of the immune system and promote genetic variation at immunity genes. This work is proceeding on two major fronts. First, through a NERC-UK project grant to T. Little, we are using the wealth of knowledge of insect immune systems to probe the Daphnia genome and EST libraries for candidate immunity genes. Once annotated, a pan-north American sample of D. pulex is used to test these genes for the molecular signature of natural, especially parasite-mediated, selection. Second, through a Wellcome Trust Senior Research Fellowship to T. Little, we are using QTL and microarray analysis to determine the genetic basis of quantitative variation in natural populations of D. pulex from Oregon. Once a range of putative genetic loci have been thoroughly detailed, we aim to explicitly track parasite-mediated genetic dynamics in response to the epidemic and endemic disease that are abundant in natural populations of Daphnia.