The chemical composition of human cerebrospinal fluid (CSF) is considered to reflect brain metabolism. In this study we measured malondialdehyde (MDA) levels and the activity of enzymes involved in antioxidative processes, glutathione reductase and glutathione peroxidase, in human cerebrospinal fluid of multiple-sclerosis (MS) patients and normal healthy volunteers. Our results indicated that the cerebrospinal fluid in MS showed significantly higher endogenous levels of MDA than the control, as well as a much greater resistance to in-vitro stimulation test. In addition, we found the activity of GSH reductase significantly increased, about twice the control values, whereas the activity of glutathione peroxidase was markedly decreased as compared to control values. Our findings suggest that in MS the activity of antioxidant enzymes is modified, and indicates the conceivable possibility of a pathogenic role of oxidative stress in the determinism of the disease.