There is evidence that a higher incidence of diverse neurodegenerative diseases is associated with the apolipoprotein E epsilon4 allele (ApoE4). Most recently it has been found that the ApoE4 allele is specifically related to an accelerated hippocampal atrophy in patients with Alzheimer's disease. Therefore, the aim of the present study was to investigate the association between ApoE4 genotypes and brain hippocampal volume reduction in alcoholics by using volumetric high-resolution MR imaging. In the present study, female alcoholics with the ApoE4 genotype were found to have significantly smaller hippocampal volumes than those not carrying an epsilon4 allele (ANOVA, p < 0.05), whereas no differences in hippocampal volume were seen in male alcoholics. Since hippocampal volume reduction is lately discussed to be proportional to brain atrophy, we propose that the alcohol-related brain atrophy in patients suffering from chronic alcoholism, is more pronounced in female carriers of the apoE epsilon4 allele. These findings indicate a genetic disposition for alcohol related brain atrophy in female carrying the ApoE4 genotype, which may also explain why female alcoholics are more susceptible to alcohol-induced brain damage.