We describe two homeobox sequences, TgHbox5 and TgHbox6, isolated from the Hawaiian sea urchin Tripneustes gratilla using a Drosophila Sex combs reduced probe. Sequence analysis shows that the encoded TgHbox5 homeodomain shares only 30-52% amino acid identity with homeodomains encoded by previously characterized genes, establishing that it is a divergent homeobox that is not in any known class of homeoboxes. TgHbox5 is expressed in the embryo as two major developmentally regulated transcripts. one at 5.0 kilobase (kb) appearing by blastula stage and the other at 2.7 kb appearing at pluteus stage. Multiple transcripts from TgHbox5 are present at a much lower level in adult tissues and are predominantly expressed in small and large intestines. The TgHbox6 homeobox is an Antenna-pedia-class homeobox, which appears not to be expressed during embryogenesis but produces abundant 3.6 and 3.2 kb transcripts in the six adult tissues examined.