Homeobox genes play important roles in animal development. We isolated a chick homeobox gene, cbx, and studied its function during embryonic development. The deduced Cbx protein contained 376 amino acid residues. Its homeodomain was related (with 65-71% sequence identity) to that of human Crx, human Cart-1, and chick Alx-4. On searching the human genome sequence, a human homologue was found, which had 78% overall sequence identity and a 100% identical homeodomain. In the developing chick retina, cbx was expressed in a small fraction of post-mitotic cells residing at anatomical locations typical of bipolar cells. These cells were Goalpha(+) and protein kinase C(-), suggesting that they were probably cone bipolar cells. cbx mRNA was also detected outside the retina, particularly in the tectum and Rathke's pouch. Replication-competent retrovirus was used to drive misexpression of cbx and of an Engrailed repression construct. Engrailed-mediated repression of Cbx was embryonic lethal, while misexpression of cbx itself was tolerated. In the retina, misexpression of cbx resulted in fewer PKC(+) bipolar cells. Our data suggest that cbx is essential for embryonic survival and may participate in the development of bipolar, probably cone bipolar, cells in the retina.