Any theory of Drosophila sex determination must explain how the X-to-autosome (X:A) ratio is read and how this information is transmitted to the genes controlling the male or female phenotypes. Although we do not yet know the intimate mechanisms by which the X:A ratio is made known to the cells, research in the past two decades has revolutionized our view of Drosophila sex determination. Much of this research has focused on the identification and analysis of the genes that are necessary for sexual differentiation and the placement of those genes in a developmental sequence. Several genes with roles in sex determination have been found. Loss-of-function mutations in most of these genes—Sex-lethal (Sxl), transformer (tra), and transformer-2 (tra2)—transform XX individuals into males. Such mutations have no effect on sex determination in XY males. Homozygosity of the intersex (ix) gene causes XX flies to develop an intersex phenotype having portions of male and female tissue in the same organ. The doublesex (dsx) gene is important for the sexual differentiation of both sexes. If dsx is absent, both XX and XY flies turn into intersexes (Baker and Ridge 1980; Belote et al. 1985a). The positioning of these genes in a developmental pathway is based on (1) the interpretation of genetic crosses resulting in flies bearing two or more of these mutations and (2) the determination of what happens when there is a complete absence of the products of one of these genes. Such studies have generated the model of the regulatory cascade.