Somatic muscle is derived from a subset of embryonic mesoderm. In Drosophila, Twist (Twi), a basic helix-loop-helix transcription factor, is a candidate regulator of mesodermal differentiation and myogenesis. Altering amounts of Twist after gastrulation revealed that high levels of Twist are required for somatic myogenesis and block the formation of other mesodermal derivatives. Expression of twist in the ectoderm drives these cells into myogenesis. Thus, after an initial role in gastrulation, twist regulates mesodermal differentiation and propels a specific subset of mesodermal cells into somatic myogenesis. Vertebrate homologs of twist may also participate in the subdivision of mesoderm.