The types of neurotrophin receptors that are expressed in neuroblastomas have different prognostic implications; trkA is a marker of good prognosis, whereas trkB expression is associated with poor prognosis. This suggests that either the signaling that is mediated via these receptors modulates the biological features of neuroblastoma cells differently, or that distinct lineages of sympathoadrenal precursors have been transformed. In this report, we evaluate the biological effects after activation of trkA or trkB by their major ligands in SH-SY5Y human neuroblastoma cells. Both trkA and trkB induce differentiation, inhibit growth, and promote the survival of cells under conditions of nutrient deprivation. However, the up-regulation of insulin-like growth factor-II (IGF-II) expression is a predominant feature of trkA activation by nerve growth factor (NGF). The growth inhibition induced by blocking the insulin-like growth factor-I receptor suggests that IGF-II is a component of the effector mechanism of trkA activation by NGF in trkA-transfected cells. Although trkA and trkB expression is associated with different prognoses in neuroblastoma, our study indicates that the effects mediated by these receptors in vivo may be quite similar for certain subsets of neuroblastomas.