ABSTRACT The limb muscles of vertebrates are derived from precursor cells that migrate from the lateral edge of the dermomyotome into the limb bud. Previous studies have shown that the paired domain-containing transcription factor Pax-3 is expressed in the limb in cells that are precursors for limb muscles (Williams, B. and Ordahl, C. P. (1994) Development 120, 785–796). In splotch (Pax-3–) embryos, the limb muscles fail to develop and cells expressing Pax-3 are no longer found in the limb. In this paper we have analyzed the role of Pax-3 in the migration and subsequent differentiation of limb muscle precursors. By labeling somites adjacent to the prospective forelimb with the lipophilic dye DiI, we have shown that cells derived from these somites do not migrate into the limbs of splotch mice. The failure of limb muscle precursors to invade the limb in splotch mice is associated with the absence of c-met expression in premigratory cells, together with a change in the morphology of the ventral dermomyotome. In addition, we have shown the lateral half of somites derived from day E9.25 splotch embryos can undergo muscle differentiation when grafted into the limb bud of stage 20 chick host embryos. Our results indicate that Pax-3 regulates the migration of limb muscle precursors into the limb and is not required for cells in the lateral somite to differentiate into muscle.