BACKGROUND: Elevated homocysteine plasma levels are considered as a risk factor for the occurrence of seizures during alcohol withdrawal. Homocysteine plasma concentrations seem to be influenced by the methylenetetrahydrofolate reductase (MTHFR) C677T-polymorphism. It was investigated whether the T-allele of the MTHFR C677T-polymorphism is associated with alcohol dependence, alcohol withdrawal seizure (WS), or the daily amount of alcohol consumption. METHODS: A group of 102 healthy controls and 221 alcoholic patients, including 97 patients with a history of mild withdrawal symptoms (MWS) and 70 patients with a history of alcohol WS, were genotyped, and personal data were collected for statistical evaluation in a case-control design. RESULTS: The T-allele is significantly associated with WS by comparing alcoholic patients with a history of WS (T-allele frequency: 0.39) and healthy controls (T-allele frequency: 0.28) (p=0.03). Although there was no significant difference between alcoholic patients with only MWS and alcoholic patients with a history of WS, a trend for the T-allele frequency among the analyzed subgroups was noticed: T-allele frequency increased from f(T)=0.28 in healthy controls to f(T)=0.33 in alcoholic patients with MWS up to f(T)=0.40 in alcohol-dependent men having a WS. Differences between healthy male controls and male alcoholic patients concerning the T-allele frequency also turned out to be significant [f(T)=0.27 vs f(T)=0.37; p=0.03]. Daily alcohol intake was independent of T-allele carrier status in alcohol-dependent patients. CONCLUSION: The present study suggests an influence of the MTHFR C677T-polymorphism on the etiology of alcohol WS and alcohol dependence in men in a western European population. An influence of MTHFR C677T on the daily amount of alcohol intake before admission among alcohol-dependent patients could not be shown.