The extracellular domains of the TrkA and TrkB neurotrophin receptors contain defined structural modules such as immunoglobulin-like domains and leucine-rich motifs (LRMs) [Schneider and Schweiger, Oncogene 6 (1991) 1807-1811]. Recently, the second LRM of TrkA was identified as a functional nerve growth factor (NGF) binding site [Windisch et al, J. Biol. chem. (1995) in press]. A peptide corresponding to this region effectively bound NGF and blocked binding of NGF to the recombinant extracellular domain of TrkA. The corresponding TrkB peptide exhibited the same effects with respect to brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4), indicating that all three TrkB ligands utilize this same binding site. Isolated LRMs therefore embody independent functional entities.