Recent work has demonstrated that induced neurite outgrowth in neuroblastoma cells and spontaneous differentiation of primary neurons in culture are accompanied by upregulation of GM1 ganglioside in the nuclear envelope. Previous reports have depicted morphological variations in the nature of stimulated neurites resulting from different neuritogenic agents, and a recent study by this laboratory demonstrated that such stimulants could be divided into two categories: those which induce axon-like neurites (group I) as opposed to those that stimulate dendrite-like outgrowths (group II). The former includes KCl, ionomycin, neuraminidase, and cholera toxin B subunit (all agents which elevate intracellular Ca2+), while the latter group is comprised of retinoic acid, dibutyryl cAMP, exogenous GM1, and low serum treatment. The present study was undertaken to determine whether differences in neuritic phenotype could be correlated with upregulation of nuclear GM1. The neuroblastoma x glioma NG108-15 cell line was employed because of its ability to respond robustly to a variety of neuritogenic stimuli. It was found that although both groups of stimulants are capable of inducing stable neurites (terminal differentiation) in this cell line, nuclear GM1 is elevated only in the presence of group I stimulants. Thus, a correlation is indicated between axonogenesis and upregulation of GM1 in the nuclear envelope. Additionally, these two events appear to coincide with elevation of intracellular Ca2+. Conversion of cells to the differentiated phenotype, with or without nuclear GM1 elevation, was found to depend in some cases on concentration of stimulant and duration of treatment.