Genetic modification of mosquitoes offers exciting possibilities for controlling malaria, but success will depend on how transformation affects the fitness of modified insects. The expression of an exogenous gene, the mutations caused by its insertion, and inbreeding while transformed lines are established can all lead to reductions in fitness. Factors influencing fitness were investigated in cage experiments with four lines of transgenic Anopheles stephensi, a vector species of human malaria. The results indicate direct costs of the introduced transgene in at least three out of the four lines, as well as an apparent cost of the inbreeding involved in making transgenic homozygotes.