As part of an ongoing examination of the functions of the fibroblast growth factor (FGF) gene family in mammalian development, we have carried out an RNA in situ hybridization analysis of the Fgf-6 gene in the mouse embryo. In contrast to what has been found for three other members of the FGF gene family, no Fgf-6 RNA was detected in mouse embryos at E6.5 through E8.5. Fgf-6 RNA was first detected in embryos at E9.5 and was localized exclusively in the myotomal compartment of the somite. Similar results were obtained with embryos at E10.5 and E11.5. At E12.5, expression was still detected in the myotome, and also in the region containing the developing muscles of the body wall. By E14.5, Fgf-6 RNA was found in the majority of skeletal muscles in the fetus. These results are discussed in comparison with what is known about the expression patterns of the genes encoding other FGF family members, as well as their high-affinity receptors.