The properties of mutations of the homoeotic gene extra sex combs (esc) indicate that the product of this gene is required early in development for correctly initiating segmental determination. Specifically, the esc⁺ gene product appears to be a necessary component of the process by which other homoeotic genes, such as those of the bithorax complex, are selectively turned on, or off, in particular segmental primordia. The resulting combinations of active and inactive genes established at this time then maintain the specific pathways of development followed subsequently by the different segments.