Fgf6, a member of the Fibroblast Growth Factor (FGF) family, is developmentally regulated and its expression is highly restricted in the adult. To gain further insight into the role of Fgf6, we studied its expression during embryogenesis using RNA in situ hybridization. Fgf6 expression is restricted to developing skeletal muscle. Fgf6 transcripts are first detected in the somites at 9.5 days post-conceptus, and expression continues in developing skeletal muscles up to at least 16.5 days post-conceptus. Fgfr4 is a putative receptor for FGF6. Its pattern of expression during myogenesis overlaps that of Fgf6, but both genes are not expressed in exactly the same population of cells. In addition, recombinant FGF6 protein is able to repress the terminal differentiation of myoblasts in culture, providing additional support to the concept that FGF6 plays an important role in myogenesis.