Millimolar concentrations of ascorbate in the presence of iron can cause neuronal cell death. This study shows that the human neuronal cell line IMR-32 is sensitive to ascorbate and that cytotoxicity can be blocked by the antioxidant enzymes Cu/Zn-superoxide dismutase and catalase. There was a selective loss of neurofilament proteins after exposure to 5 or 10 mM ascorbate, as assessed by immunostaining and by Western blotting. Loss of actin or tubulin was not seen, suggesting that loss of neurofilaments is a sensitive and selective marker for free radical damage in these cells.