In this study, it is reported that neonatal murine microglia and N9 murine microglial cell line express tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL). TRAIL protein and mRNA expression in murine microglia greatly upregulate upon stimulation with interferon gamma (IFNgamma) or lipopolysaccharide (LPS) as revealed by immunoprecipitation-immunoblotting, reverse transcriptase-polymerase chain reaction (RT-PCR) and flow cytometry techniques. IFNgamma and LPS act synergistically to induce TRAIL expression on both translational and transcriptional levels. The upregulated microglial TRAIL in inflammatory conditions may involve in the cytotoxic effect of these cells and play a role in neurodegenerative processes.