Neuroblastoma cells maintained in serum-free medium exhibit a significant induction of MAP-1a and Tau proteins, but not MAP-2; the time course of these inductions is highly correlated with an increase in microtubule mass which parallels neurite growth. Bovine brain gangliosides (BBG) enhance the neurite outgrowth response of these cells. We report here that one effect of gangliosides is the selective and dramatic induction of MAP-2 expression. Our results also indicate a strong parallelism between this induction and the increase in microtubule mass which accompanies the appearance of more numerous, longer, and highly branched neurites. These observations suggest that MAP-2 induction in neuroblastoma cells may lead to a further differentiation of neurites equivalent to that observed in mature brain neurons. Finally, our results indicate that gangliosides per se are not neuritogenic factors but rather substances capable of enhancing cell- derived influences which affect the neurite outgrowth response of neuroblastoma cells and the type of MAP that they express.