We studied the effects of nerve growth factor (NGF) to determine whether neuroblastoma (NB) cells share the pattern of altered response to growth regulatory factors shown by various malignant transformed cells. NGF induces neurite outgrowth, arrests growth, and enhances survival in normal neurons and in the rat pheochromocytoma, a tumor cell closely related to NB. With respect to neurite outgrowth, lines SK-N-SH, SH-SY5Y, LA-N-5, and CHP-126 were sensitive, IMR-32 was resistant, and SH-EP1, SK-N-MC, MC-IXC, CHP-100, and CHP-134 were unresponsive. Conditioned media from unresponsive cells did not inhibit response in sensitive cells. Unexpectedly, NGF neither reduced the growth rate nor enhanced survival in any NB cell line. Conditioned medium from all NB cell lines enhanced 125I-NGF binding in embryonic sensory cells. Regulation of growth rate and neurite outgrowth, then, are separable. A fundamental defect in NB may be the acquisition of a capacity for growth and survival independent of NGF. 125I-NGF was bound to both Fast and Slow receptors in MC-IXC cells, but only to Slow receptors in NGF-responsive SH-SY5Y and LA-N-5 cells, showing Fast receptors are not required for neurite outgrowth. Independence from NGF-regulated growth and survival is unexplainable by an absence of NGF receptors.