Homeosis refers to a class of mutations which beings about the replacement of one body part with that of another normally found elsewhere on the animal. Molecular analysis of the Drosophila homeotic regulatory genes has shown that the proteins which they encode contain a highly conserved 60 amino acid domain (the homeo domain). Homeo domain containing proteins are part of the mechanism which controls the diversity of body parts in Drosophila. The significance of the homeo domain has been highlighted by the recent demonstration that homeo domain proteins are found in other metazoans, including mice and humans. These observations suggest the exciting possibility that genes which control insect body plan may have partial homology to functionally related genes which control the body plans of mammals. By identifying the functional roles these genes play in mouse development, we hope to gain insight into the basic principles which govern mammalian development. As an initial step, we have focused our efforts on the molecular biology of the murine Hox 1.3 homeo box gene and its encoded protein. DNA sequence analysis of Hox 1.3 cDNA and genomic clones indicates that the gene is organized into two exons and encodes a 270 amino acid homeo domain protein. Messenger RNA analysis shows that the gene is expressed early in embryogenesis. Hox 1.3 transcripts are also present in many adult tissues which possess different cell lineages. Immunolocalization studies detect the Hox 1.3 protein in many cell types during embryonic development, most notably in the spinal ganglia. In the adult CNS, certain subsets of fully differentiated neurons express the Hox 1.3 protein. The Purkinje neurons of the cerebellum, the pyramidal and dentate neurons of the hippocampus, and the motor neurons of the spinal cord are positive.