What determines whether a mosquito develops as a male or a female is largely unknown. This question is not just an academic curiosity. Only female mosquitoes feed on vertebrate blood and hence are capable of transmitting disease. And the variety of diseases transmitted by mosquitoes is staggering. This proposal focuses on the Anopheles mosquitoes that transmit malaria but mosquitoes also transmit a number or incurable viruses as well as a number of severe parasitic diseases of humans and animals. We will use a variety or approaches to disclose the processes that trigger the sex development of Anopheles mosquitoes. We have already identified one gene, doublesex, which switches on a different chain of events in males and females. Based on studies in other insects, and our own preliminary data, we believe that this gene is a key regulator of sexual differentiation. In this proposal we will use doublesex as an anchor to identify steps upstream and downstream of the sex differentiation pathway and thereby begin to build a picture of the sex determination process in mosquitoes. We believe that this pathway will prove to be a rich source of targets for novel mosquito intervention strategies.