Based on pharmacologic evidence, it has been suggested that GABA(B) receptors may play a crucial role in the generation of alpha-electroencephalogram (EEG) oscillations. We tested whether three exonic variants of the gene encoding the human GABA(B) receptor (GABA(B)R1) modify scalp-recorded alpha-EEG voltage. One hundred twenty-eight patients suffering from alcoholism and 114 normal subjects were investigated. Alcohol-dependent patients were included because evidence exists that the frequently observed alpha low voltage in these subjects is at least partly a trait variable. Logistic regression analyses revealed no associations between alpha-EEG voltage and polymorphic variations in exon 1a1 or exon 11. A significant interaction was observed for an exon 7 substitution polymorphism and diagnosis (P = 0.009). Post hoc analyses showed an association between EEG phenotype and exon 7 genotype in normal subjects only. It is concluded that this particular association may only be observable under physiologic conditions and that alpha low voltage in alcohol-dependent subjects is under the control of either different genes or that it is related to the disease process.