Chronic alcohol consumption can induce brain atrophy, whereby the exact mechanism of brain damage in alcoholics remains unknown. There is evidence that chronic alcoholism is associated with hyperhomocysteinemia. Homocysteine is an excitatory amino acid which markedly enhances the vulnerability of neuronal cells to excitotoxic and oxidative injury in vitro and in vivo. The present volumetric magnetic resonance imaging study included 52 chronic alcoholics and 30 non-drinking healthy controls. Patients were active drinkers and had an established diagnosis of alcohol dependence. We investigated the influence of different variables on the hippocampal volume of patients suffering from chronic alcoholism. We observed that pathological raised levels of plasma homocysteine showed the most significant correlation to hippocampal volume reduction (P<0.001, multiple regression analysis). Raised plasma levels of homocysteine are associated with hippocampal (brain) atrophy in alcoholism.