Neurofibrillary tangles (NFTs) composed mostly of the protein tau characterize many neurodegenerative diseases including Alzheimer's disease (AD). Impaired nerve growth factor (NGF) signaling has been linked to the neurodegeneration in AD. It is important to study the NGF-mediated regulation of tau in a human cell line that can produce NFTs to better understand what may lead to this pathology. The present study characterized NGF signaling pathways and their modulation by nitric oxide synthase (NOS) inhibitors in IMR32 human neuroblastoma cells. NGF-mediated activation of Akt is rapid and transient but is prolonged by inhibition of the MAP kinase pathway or NOS. MAP kinase is also rapidly activated by NGF and its phosphorylation is also prolonged by NOS inhibitors. In addition this study demonstrated that tau protein levels are increased by NGF and that inhibition of the MAP kinase pathway attuates NGF-mediated increases in tau transcription.