We analysed the expression of four mouse homeobox genes related to two Drosophila genes expressed in the developing head of the fly: Emx1 and Emx2, related to empty spiracles and Otx1 and Otx2, related to orthodenticle. The four genes are all expressed in the developing rostral brain of E10 mouse embryos in a specific manner. Otx2 is expressed in every dorsal and most ventral regions of telencephalon, diencephalon and mesencephalon. The Otx1 expression domain is similar to that of Otx2, but contained within it. The Emx2 expression domain is comprised of dorsal telencephalon and small diencephalic regions, both dorsally and ventrally. Finally, Emx1 expression is exclusively confined to the dorsal telencephalon. Thus, at this stage the expression domains of the four genes appear to be continuous regions contained within each other in the sequence Emx1 < Emx2 < Otx1 < Otx2. The first appearance of transcripts of these genes is also sequential: Otx2 is expressed first (E5.5), followed by Otx1 and Emx2 (E8-8.5) and finally by Emx1 (E9.5). These findings suggest a role of the four genes in establishing cell fates within the limits of the various embryonic brain regions in a discrete progressive process with its center in the dorsal telencephalon. The structural organization and the regulation of these genes appear remarkably conserved in evolution.