Mice that have mutations in both myogenic transcription factors Myf-5 and MyoD totally lack skeletal muscle fibres and their precursor myoblasts, whereas with either mutation alone, muscle is present. Skeletal muscle in the vertebrate body is derived from epithelial somites that respond to environmental signals to form the dorsal epithelial dermomyotome (dermis, muscle) and ventral mesenchymal sclerotome (axial skeleton, ribs). The first muscle, the myotome, forms centrally in the somite, when only myf-5 is programming myogenesis. By targeting the nlacZ reporter gene into the myf-5 locus, we demonstrate that beta-galactosidase+ muscle progenitor cells are present in the dermomyotome of myf-5 null embryos, and that they undergo a normal epithelial-mesenchymal transition; however, they migrate aberrantly. Dorsally, they accumulate under the ectoderm and express a non-muscle dermal marker, Dermo-1. Ventrally, beta-galactosidase+ cells also fail to localize correctly, express a cartilage marker scleraxis, and are subsequently found in ribs. Therefore Myf-5 protein is necessary for cells to respond correctly to positional cues in the embryo and to adopt their myogenic fate. In its absence, muscle progenitors, having activated myf-5, remain multipotent and differentiate into other somitic derivatives according to their local environment.