We show that neurotrophins acting at the growth cone via Trk receptors can mediate rapid and distinct changes in growth cone response to collapsin-1, an inhibitory axon guidance molecule. We find that the sensitivity of growth cones of dorsal root ganglia (DRG) neurons to collapsin-1 differs when chronically cultured in BDNF, NT-3, or NGF with those in BDNF most sensitive and those in NGF least sensitive. Further, growth cones chronically cultured in BDNF rapidly decrease their sensitivity to collapsin-1 with acute exposure to NGF. Conversely, growth cones chronically cultured in NGF rapidly increase their sensitivity to collapsin-1 with acute exposure to BDNF. These bidirectional effects of neurotrophins appear to be mediated by the neurotrophin-specific Trk receptors on the growth cones since most growth cones are immunopositive for TrkA and TrkB, the NGF and BDNF receptors, respectively, and k252a, a selective inhibitor of Trk-mediated responses to neurotrophins, diminishes collapsin-1-induced growth cone collapse. These findings indicate that the response of growth cones to axon guidance molecules is dynamic and can be rapidly and differentially modulated by neurotrophins.