: Intracellular Wolbachia bacteria infect a diverse range of invertebrate hosts, including medically important disease vectors. Many Wolbachia infections cause cytoplasmic incompatibility, which effectively sterilizes mating between host individuals that harbor differing infection types. We have recently developed a model that defines the relationship between the Wolbachia infection frequency and host population size. Model simulations predict a novel strategy for suppressing insect populations. This strategy is based upon artificially prolonging an unstable coexistence that occurs when two or more incompatible Wolbachia types infect a host population, resulting in host population suppression. As Wolbachia occurs naturally within a broad range of invertebrates, this strategy is potentially applicable to a variety of medically and economically important systems. In addition to population suppression strategies, population replacement strategies propose to employ Wolbachia as a vehicle for spreading desired genotypes (e.g., refractoriness to disease transmission) into vector populations. In the outlined research, we will develop, test and evaluate population suppression and replacement strategies predicted by model simulations in populations of the vector mosquito Culex pipiens. Cx. pipiens has been selected as the initial target due to its importance as a disease vector and the availability of multiple, incompatible Wolbachia infections in naturally occurring Culex populations. Additional experiments will examine strategies for retarding, arresting or reversing Wolbachia-based population replacement. The latter strategies represent an appropriate safeguard that may prove necessary if unexpected, negative consequences become associated with population replacement. To improve strategy design, implementation, and evaluation, aims will include better defining the infection dynamics of the Culex/Wolbachia symbiosis (e.g., maternal transmission rates and Wolbachia effects on host fitness), simplifying discrimination between Culex infection types, and improving methods for field cage evaluation of Wolbachia control strategies.