Six human neuroblastoma (NB) cell lines of different type: three neuronal, one mixed and two epithelial, were studied for their responsiveness to interferon gamma (IFNgamma). The effects of IFNgamma on cell growth rate and morphology were first evaluated: the replication was significantly inhibited in five out of six NB, while a neural morphological maturation was evident only in the three neural NB. Whether IFNgamma could also control the synthesis of two extracellular matrix glycoproteins, often involved in NB differentiation, laminin (LM) and fibronectin (FN), was then analyzed. Both glycoproteins increased after IFNgamma treatment in all neural and in the mixed NB, while they slightly decreased in one and did not change significantly in the other epithelial NB. Therefore, IFNgamma determines the up-regulation of FN and LM, while inducing NB cell growth inhibition and neural differentiation. These data support the hypothesis that the expression of the two extracellular matrix glycoproteins is controlled by IFNgamma during the complex event of NB terminal maturation.