We have isolated two genes, Hox-2.8 and Hox-2.9, from the mouse homeobox cluster Hox-2, located on chromosome 11. A 120-kilobase yeast artificial chromosome (YAC) containing a large region of the murine Hox-2 cluster, including 45 kilobases of sequence upstream of the most 5' gene, was cloned. The DNA sequence of the YAC is unrearranged relative to the genomic map. We have subcloned from the YAC insert a homeobox gene, Hox-2.8, whose homeodolmain is highly related to that of the Drosophila homeotic gene proboscopedia (pb). The expression pattern of Hox-2.8 during embryogenesis extends the trend established by genes from Hox-2.5 to -2.7 of successively anterior domains of expression in the neural tube. We have also subcloned and sequenced from a cosmid the labial (lab)-related Hox-2.9, the most 3' member of the cluster to date. These data lend further support to the idea of a common evolutionary origin of the mouse Hox and Drosophila HOM clusters. The YAC will enable us to construct modified forms of the Hox-2 cluster in yeast and to identify their effect on the phenotype of the animal in transgenic mouse strains.