The bHLH (basic helix-loop-helix) transcription factor, sea urchin myogenic factor-1 (SUM-1), plays an important role in myogenic determination during sea urchin embryogenesis. SUM-1-mediated transactivation is restricted to the mesenchyme lineages in transgenic sea urchin embryos, suggesting that other factors, either positive or negative, influence the activity of SUM-1 in different embryonic cell types. While post-translational regulation of vertebrate myogenic factors has been suggested from in vitro studies, it has never been demonstrated in vivo. The most compelling in vitro experiments have shown that the mesodermal bHLH, twist, negatively regulates myogenic bHLHs. However, in the vertebrate embryo, twist and myogenic bHLHs are not expressed coincidentally, and different concentrations of twist play a role in the differentiation of different muscle lineages (somatic versus visceral) in Drosophila embryos. The gene expression studies in vertebrates and the genetic experiments in Drosophila suggest disparate roles for twist in these organisms. To gain a better understanding of the role of twist in mesodermal and myogenic specification, we cloned a sea urchin twist homologue and characterized its role in gastrulation and myogenesis in this simple embryo. Our data suggest that twist from Lytechinus variegatus functions after gastrulation and initial specification of the embryonic mesoderm of the sea urchin.