The genetic cascades regulating sex determination of the housefly, Musca domestica, and the fruitfly, Drosophila melanogaster, appear strikingly different. The bifunctional switch gene doublesex, however, is present at the bottom of the regulatory cascades of both species, and so is transformer-2, one of the genetic elements required for the sex-specific regulation of doublesex. The upstream regulators are different: Drosophila utilizes Sex-lethal to coordinate the control of sex determination and dosage compensation, i.e., the process that equilibrates the difference of two X chromosomes in females versus one X chromosome in males. In the housefly, Sex-lethal is not involved in sex determination, and dosage compensation, if existent at all, is not coupled with sexual differentiation. This allows for more adaptive plasticity in the housefly system. Accordingly, natural housefly populations can vary greatly in their mechanism of sex determination, and new types can be generated in the laboratory.