We examine the constraints and the feasibility of field experiments involving the release of genetically modified (GM) pathogen-resistant mosquitoes, and whether there are alternatives to the research line based on the production of refractory strains. The production of a GM mosquito strain characterized instead by obligate primiparous and parous autogeny and by disrupted host seeking and biting behaviour could make the release more acceptable by the general public. Genetic transformation should act in this case to reverse some of the essential steps of the evolutionary process that gave rise to hematophagy. The replacement strategy could be based on the mass release of both sexes in a well defined ecological niche made temporarily empty of the natural population, thus avoiding the problems related to the need of sexual competitiveness of the released material. This option is encouraged by the growing evidence that competitive exclusion mechanisms influence the pattern of distribution of different taxa within Anopheles gambiae s.s. and by the fact that the plesiomorphic characteristics of vitellogenesis without a blood meal (autogeny), which exploits fat body reserve accumulated during larval life and food other than blood in adult life, persist as genetic variants in various hematophagous insect groups, and it has been found secondarily fixed in others showing stable reversions to primiparous and parous autogeny. If this has been the result of natural selection, then the artificial production of non-biting mosquito strains, by selection and/or transgenesis, should be feasible.