Nerve growth factor (NGF) plays a trophic and tropic role in the development of vertebrate sympathetic and sensory ganglia; however, the precise nature of the NGF effect(s) is not understood. Study of NGF-responsive human neuroblastoma cell lines allows characterization of NGF-induced neurite outgrowth in cells not dependent on NGF for survival. The human neuroblastoma line SK-N-SH did not significantly extend neurites in response to NGF, but did show an increase in cell number. By contrast, a clone of the line, SH-IN, extended neurites in response to NGF or dibutyryl cyclic AMP, and showed inhibition of cell proliferation. Thus, cells capable of morphological differentiation in response to NGF can be cloned from neuroblastoma cell lines in which the majority of the cells fail to extend neurites even in the presence of NGF.