BACKGROUND: Alpha-tocopherol (alpha -tocopherol) can effectively relieve neuronal damage induced by oxygen-centered free radicals. However, the effective dose remains controversial. OBJECTIVE: To evaluate the protective effects of low-concentration a -tocopherol on neuronal membranes. DESIGN, TIME AND SETTING: Contrast observation and in vitro study, performed at Laboratory of Neurosurgery, Tianjin Huanhu Hospital between April and September 2006. MATERIALS: Fetal cortical neurons were derived from two 14-day pregnant SD rats, and alpha -tocopherol was provided by Sigma, USA. METHODS: The neurons were randomly assigned to six groups: (1) normal: neurons were cultured under normal conditions; (2) oxidative damage: oxidative free radicals was damaged using the Fenton reaction; (3) alpha -tocopherol: neurons were cultured in different concentrations of a -tocopherol 10, 20, 40, and 80 mg/L for 2 hours, respectively. MAIN OUTCOME MEASURES: Neuronal membrane damage was observed using a confocal laser microscope, and malonaldehyde production was detected using the thiobarbituric acid method. RESULTS: At normal, biological concentrations (10 mg/L), alpha -tocopherol induced no change in the damaged neurons (P > 0.05). However, at a concentration of 80 mg/L, the number of damaged neurons was significantly reduced, compared with the damage group (P < 0.05). Malonaldehyde levels following 80 mg/L alpha -tocopherol treatment were less than the oxygen free radical damage group (P < 0.05), but greater than the control group (P < 0.01). CONCLUSION: A concentration of 80 mg/L alpha -tocopherol can effectively protect the neuronal cell membrane from oxidative damage.