The aim of this study was to investigate the role of NO-cGMP pathway in NMDA-induced NGF mRNA expression by T67 astrocytoma cells. Levels of nitrite, a breakdown product of NO, in supernatants of NMDA-treated astrocytoma cells were significantly higher compared with control cells, this effect being reversed by the specific NO synthase inhibitor L-NAME. Furthermore, NGF mRNA expression was induced by NMDA treatment, this effect being inhibited by pretreating cells with L-NAME. Moreover, methylene blue, an inhibitor of NO biological activity at guanylate cyclase level, inhibited NMDA-induced NGF mRNA expression and this effect was reversed by dbt2-cGMP. These findings suggest that NO-cGMP pathway mediates the synthesis of NGF mRNA.