The possible involvement of tenascin-C in the reinnervation of a skeletal muscle was investigated in the tenascin-C-deficient mouse (T–/–) produced by Saga et al.(1992; Genes Dev 6: 1821–1831). The pattern of reinnervation, observed after denervation of the triangularis sterni muscle, differs in T–/–and wild-type muscles in several traits. Axonal growth and stability of terminal arbors are impaired in the T–/–muscle: Some axons in mutant muscles grow beyond their original targets and reinnervate other synaptic sites, which may become dually innervated. In contrast to wild type, polyinnervation increases with time after denervation in T–/–muscles and is still present 7 months after nerve crush. The expression of a tenascin-C mRNA product disappears between 1 and 2 months after nerve crush. Of interest is that this transcriptional regulation in T–/–muscles occurs when major alterations in the morphology of regenerating endings become obvious. These observations strongly implicate tenascin-C in the formation, maturation, and stabilization of the neuromuscular junction.© 2002 Wiley-Liss, Inc.