Oxidative stress and glutamate-mediated toxicity may play an important role in the etiopathogenesis of amyotrophic lateral sclerosis (ALS). The vascular endothelial growth factor (VEGF) is a neuroprotective cytokine activated by hypoxia. The aim of this study was to measure VEGF levels in the cerebrospinal fluid (CSF) of ALS patients. The study concerned 30 ALS patients and 30 control subjects. The VEGF was measured by the enzyme-linked immunosorbent assay. The results have shown that CSF VEGF levels are significantly increased in patients with long duration of ALS and in patients with limb-onset of the disease compared with controls (P < 0.05). Moreover, the type of ALS patients' subgroup significantly influences CSF VEGF levels (P = 0.05). The CSF VEGF levels were significantly increased in patients with limb-onset compared to patients with bulbar-onset of ALS, and in patients with long duration of ALS compared to patients with its short duration (P < 0.05). There was a significant correlation between CSF VEGF levels and duration of ALS (P < 0.05). It seems that a significant increase in CSF VEGF levels in patients with limb-onset of ALS and in patients with long duration of the disease may have a protective role against glutamate-mediated toxicity and oxidative damage of motor neurons. However, the conclusions are limited due to relatively small subgroups of ALS patients and by lack of a control group consisting of healthy persons. Further investigations could help to confirm the results from this preliminary report.