THE trkC gene(1,2) is expressed throughout the mammalian nervous system(3-5) and encodes a series of tyrosine protein kinase isoforms that serve as receptors for neurotrophin-3 (NT3), a member of the nerve growth factor (NGF) family of neurotrophic factors(2,6-8). One of these isoforms, gp145(trkC)/TrkC K1, mediates the trophic properties of NT3 in cultured Cells(2,6-8). Here we show that homozygous mice defective for TrkC tyrosine protein kinase receptors lack Ia muscle afferent projections to spinal motor neurons and have fewer large myelinated axons in the dorsal root and posterior columns of the spinal cord. These mice display abnormal movements and postures, indicating that NT3/TrkC-dependent sensory neurons may play a primary role in proprioception, the sense of position and movement of the limbs.