Like other homeobox genes of the Antennapedia and bithorax complexes (collectively called the HOM complex), the Drosophila Deformed (Dfd) gene has structural homologues in the Hox/HOX complexes of mouse and humans, one of which is human HOX4B (refs 3, 4). Previous experiments indicated that HOX4B protein can specifically activate the expression of the endogenous Dfd transcription unit in Drosophila embryos and larvae. We therefore asked whether HOX4B cis-regulatory elements could mimic the function of a Dfd autoregulatory element in Drosophila embryos. Here we show that a HOX4B upstream element can surprisingly provide expression in a posterior head segment of Drosophila. One possible mechanism for the axial position-specificity of the human element may involve the conservation of a Dfd-specific autoregulatory circuit in both arthropod and chordate lineages. This possibility is supported by the finding that a Drosophila Dfd autoregulatory element supplies spatially localized expression in the hindbrain of mouse embryos.