Homocysteine is a sulfhydryl-containing amino acid derived from the essential amino acid methionine. Total Hcy plasma level varies in the range of 5-15 μmol/L in the normal population. Our aim in this study was to investigate the possible correlations among homocysteine plasma levels, oxidative stress parameters and clinical evolution of stroke. Fifty patients with large-vessel ischemic stroke were studied. Biochemical determinations were performed at entry (T0) and then repeated one month after stroke (T1). Homocysteine levels were significantly increased at T0 with respect to T1 and showed a significant positive correlation with the expression of oxidative stress markers and a negative correlation with indicators of protective anti stress activity. A significant increase of antioxidant activity occurred from T0 to T1 and changes were associated with the severity of clinical conditions. In particular, the extent of homocysteine and of oxidative stress markers plasmatic levels re- duction and of the contemporary increase in anti stress biochemical activities were associated with a reduction of NIHSS scores. These findings, besides confirming an involvement of oxidative stress in in- fluencing the evolution of stroke, suggest a role for homocysteine as a potentially modifiable biochemical alteration able to modulate some mechanisms in- volved in the production of ischemic damage.