The induction of the inducible nitric oxide synthase (iNOS) has been proposed to play a role in a variety of inflammatory diseases. Sodium salicylate (NaSal) is the most commonly used anti-inflammatory agent. We investigated whether NaSal can diminish the induction of iNOS in murine brain microglial cells. In primary cultures, interferon-γ (IFN-γ) or lipopolysaccharide (LPS) separately did not stimulate nitric oxide (NO) production, whereas IFN-γ combined with LPS synergistically induced iNOS. NaSal inhibited both the production of NO and expression of iNOS in microglial cells. Synergy between IFN-γ and LPS was mainly dependent on tumour necrosis factor-α (TNF-α) secretion as the increase of the induction of the iNOS by IFN-γ plus LPS was associated with the increase of TNF-α secretion and IFN-γ plus LPS-induced TNF-α secretion by microglial cells was decreased by the treatment with NaSal. These results suggest a possible use of NaSal in managing inflammation of the central nervous system through inhibition of the iNOS induction.