The cytokines interleukin 1 (IL-1) and tumor necrosis factor alpha (TNF-alpha), produced by glial cells within the brain, appear to contribute to the neuropathogenesis of several inflammatory neurodegenerative diseases. However, little is known about the mechanism underlying cytokine-induced neurotoxicity. Using astroglial cultures obtained from fetal rat brain, we investigated the effects of lipopolysacchanides (LPS) and cytokines (IL-1beta and TNF-alpha). Primary cell cultures treated with LPS, IL-1beta plus TNF-alpha generated substantial amounts of nitric oxide (NO), elevated interleukin 6 (IL-6) levels and caused astroglial injury measured by lactate dehydrogenase (LDH) activity. However, blockade of NO production with nitric oxide synthase (NOS) inhibitors did not affect cell death, suggesting that NO is not responsible for cytokine-induced astroglial cell death under the experimental conditions employed.