Neurocognitive disturbances suggesting a frontal lobe dysfunction have been observed in pathological gamblers and alcohol dependents. Given that a high homocysteine level has been suggested to be a mediating factor in alcohol-related cognitive decline, we have determined homocysteine and cobalamine in cerebrospinal fluid (CSF) obtained from 11 pathological male gamblers and 11 healthy male controls. Compared with healthy controls, pathological gamblers displayed higher CSF levels of homocysteine while the opposite was the case with CSF cobalamine. Smoking decreased the levels of homocysteine while the concentrations of cobalamine were increased. Homocysteine is a sulphur-containing amino acid exerting cytotoxic effects in living cells. The metabolism of homocysteine to methionine is mediated by cobalamine and folate. Human studies suggest that homocysteine plays a role in brain damage and cognitive and memory decline. The relationship between pathological gambling, homocysteine, cobalamine, folate (not determined in the study) and cognitive processing warrants further investigation.