The inducible form of nitric oxide synthase (iNOS) is an essential element of the immune response, which is expressed primarily in microglial cells within the CNS. Exposure of rat cortical neuronal cells to the pro-inflammatory bacterial endotoxin lipopolysaccharide (LPS) resulted in a significant increase in the expression of the cellular iNOS protein expression and NO generation (which serves as an indirect measure of NOS catalytic activity). These effects were potentiated by costimulation with interferon-gamma (IFNgamma) and the increase in NO generation was abolished by the iNOS selective inhibitor 1400W, although this did not attenuate the toxin-induced increase in the enzyme expression. As the cortex is one of the principal areas to be targeted in Alzheimer's disease (AD), the present findings may help to further our understanding of the biochemical events associated with the neurodegenerative process.