Segmentation in Drosophila is based on a cascade of hierarchical gene interactions initiated by maternally deposited morphogens that define the spatially restricted domains of gap gene expression at blastoderm (reviewed in ref. 1). Although segmentation of the embryonic head is morphologically obscured, the repeated patterns of expression of the segment polarity genes reflect the formation of seven head segments; two of these depend on the segmentation and homeotic genes used in the trunk, whereas the others form as a result of the activity of the head-specific genes orthodenticle (otd), empty spiracles (ems) and buttonhead (btd). The genes ems and otd encode homeodomain proteins, suggesting that they may function as transcription factors. They are expressed in overlapping stripes in the early embryonic head of Drosophila, and their vertebrate homologues, otx and emx, are expressed in overlapping domains in the anterior central nervous system of the mouse embryo. We show here that btd is expressed in a stripe covering the head analgen of the segments affected in btd lack-of-function mutants and that btd encodes a zinc-finger-type transcription factor with sequence and functional similarity to the prototype mammalian transcription factor Sp1 (ref. 9). When expressed in the spatial pattern of btd, a transgene providing Sp1 activity can support development of the mandibular segment in the head of btd mutant embryos. A ubiquitous transcription factor from humans can therefore replace an essential component of the genetic circuitry required to specify the development of a particular head segment in the fly.