We describe the extent to which presynaptic structures at the embryonic neuromuscular junction of Drosophila can form in mutants where development of postsynaptic somatic muscles is affected. Although twist mutant embryos lack mesoderm, motor axons still grow out of the CNS and form morphologically normal presynaptic active zones, independent of their target cells. In myoblast city mutant embryos, myoblasts do not fuse but form fully differentiated mononucleate muscles, which make functional neuromuscular synapses with correctly localized presynaptic active zones. Myoblasts also fail to fuse but still attract appropriate innervation in mef2 mutant embryos. However, these myoblasts fail to differentiate into muscles and presynaptic active zones fail to localize at neuromuscular contacts. Thus, the process of synapse formation can be genetically separated from the process of target recognition, revealing that localization of presynaptic active zones requires mef2-dependent muscle differentiation.