As the dopaminergic and GABAergic systems have been implicated in alcohol-related behaviors, variants of the D 2 dopamine receptor (DRD2) and GABA A receptor β3 subunit (GABRB3) genes were determined in a population-based association study of Caucasian non-alcoholic and alcoholic subjects. In severe alcoholics, compared to non-alcoholics, a significant increase was found in the prevalence ( P=1.7×10 −5) and frequency ( P=1.6×10 −5) of the DRD2 minor (A1) allele. Moreover, a significant progressive increase was observed in A1 allelic prevalence ( P=3.1×10 −6) and frequency ( P=2.7×10 −6) in the order of non-alcoholics, less severe and severe alcoholics. In severe alcoholics, compared to non-alcoholics, a significant decrease was found in the prevalence ( P=4.5×10 −3) and frequency ( P=2.7×10 −2) of the GABRB3 major (G1) allele. Furthermore, a significant progressive decrease was noted in G1 allelic prevalence ( P=2.4×10 −3) and frequency ( P=1.9×10 −2) in non-alcoholics, less severe and severe alcoholics, respectively. In sum, in the same population of non-alcoholics and alcoholics studied, variants of both the DRD2 and GABRB3 genes independently contribute to the risk for alcoholism, with the DRD2 variants revealing a stronger effect than the GABRB3 variants. However, when the DRD2 and the GABRB3 variants are combined, the risk for alcoholism is more robust than when these variants are considered separately.