AbstractNeuroblastomas are heterogeneous tumors arising from sympathetic precursors in the neural crest. Growth factor stimulation of neuroblastomas promote diverse biological responses (mitogenesis, differentiation, cell death) depending on the particular tumor studied. Here we show that brief treatment with retinoic acid (RA) rendered the human neuroblastoma lines SY5Y, NGP, SMS‐KCNR, and SK‐N‐SH dependent on brain‐derived neurotrophic factor (BDNF) for survival. The BDNF‐ and trkB‐expressing line SMS‐KCN was dependent on an autocrine BDNF/trkB survival without exposure to RA. We conclude that the BDNF/trkB pathway plays an important role in neuroblastoma survival and speculate on a possible role in tumor pathogenesis. J. Neurosci. Res. 64:355–363, 2001. © 2001 Wiley‐Liss, Inc.