The extraordinary positional conservation of the homeotic genes within the Antennapedia and the Bithorax Complexes (ANT-C and BX-C) in Drosophila melanogaster and the murine Hox and human HOX clusters of genes can be interpreted as a reflection of functional necessity. The homeotic gene proboscipedia (pb) resides within the ANT-C, and its sequence is related to that of Hox-1.5. We show that two independent pb minigene P-element insertion lines completely rescue the labial palp-to-first leg homeotic transformation caused by pb null mutations; thus, a homeotic gene of the ANT-C can properly carry out its homeotic function outside of the complex. Despite the complete rescue of the null, the minigene expresses pb protein in only a subset of pb's normal domains of expression. Therefore, the biological significance of the excluded expression pattern elements remains unclear except to note they appear unnecessary for specifying normal labial identity. Additionally, by using reporter gene constructs inserted into the Drosophila genome and by comparing pb-associated genomic sequences from two divergent species, we have located cis-acting regulatory elements required for pb expression in embryos and larvae.