Most mosquito species display host preferences that are a crucial determinant of the transmission rate of mosquito-borne pathogens. Although a transgenic approach, based on driving genes for zoophily into vector populations, has been advocated as a malaria control strategy by the World Health Organization since 1982, the genes involved in mosquito host choice remain poorly understood. Culex pipiens pallens Coquillet mosquitoes were artificially selected for two different host preferences in a specially designed experimental enclosure. Of 3,035 mosquitoes obtained from larvae and pupae collected from the wild (the F0 generation), 27% preferentially fed on pigeons and 16% fed on mice. Following artificial selection for these host preferences over successive generations, the percentage of mosquitoes that preferred to feed on pigeons or mice gradually increased, eventually stabilizing at ∼55 and 34%, respectively, after the sixth generation. Intergenerational differences in host preferences were significant (P < 0.001). Furthermore, differences in host preferences between mosquitoes selected to prefer pigeons and those selected to prefer mice were both significant and consistent over almost six generations.