One strategy for controlling malaria and other vector-borne diseases is to use transgenic mosquitoes that are refractory to the pathogen. Minimal fitness load imposed by the transgene will greatly improve the chances of success of such approach. Transgenic mosquitoes expressing the SM1 peptide driven by the blood-inducible and midgut-specific carboxypeptidase promoter are inefficient vectors in an experimental malaria model. Previous studies have shown that the SM1 transgene does not impose any detectable fitness load to the transgenic mosquito that carries it. Previous work has shown that malaria parasites reduce reproductive fitness of the mosquitoes that harvor them. We reasoned that transgenic mosquitoes that inhibit Plasmodium development may have a competitive advantage when fed on infected blood because it would have fewer or no parasites. To investigate this hypothesis, cage experiments were performed in which mixtures of SM1 transgenic and non-transgenic mosquitoes were fed at every generation with Plasmodium berghei-infected blood. Under these conditions, the transgenic mosquitoes had a significant advantage over the non-transgenic ones in that the proportion of transgenic mosquitoes increased at each generation. Further studies indicated that such advantage derives from two factors: (1) non-transgenic mosquitoes had significant higher mortality than transgenic ones when fed on infected mice, presumably due to ookinete damage to the midgut; (2) transgenic mosquitoes laid significantly more eggs than non-transgenic ones, presumably because they carried fewer parasites. The higher fecundity and lower mortality of these transgenic mosquitoes have important implications for controlling malaria via genetic modification of mosquitoes.