Malaria control schemes based on the yet untested concept of replacing vector populations with mosquitoes of the same species unable to transmit the parasite offer one more means of attacking this important public health problem. Research is underway in several laboratories aimed at defining factors that can act to interrupt the development of the malaria parasite in the mosquito host, the genetic basis for such refractory mechanisms, methods for introducing genes coding for refractory mechanisms into the mosquito genome, and methods for replacing vector populations in the field. The complexities of such an undertaking are many and varied, but the potential impact of a successful replacement strategy on the epidemiology of malaria in the target area could be significant.