The use of persons who become alcoholic despite having a well-defined negative risk for alcoholism (inactive aldehyde dehydrogenase-2 or ALDH2) is advantageous in genetic research because of this population's reduced heterogeneity and possible genetic factors conferring susceptibility to alcohol dependence. This investigation of central serotonin neurotransmission, specifically the serotonin 1B (5HT1B) receptor gene and its role in both regulating alcohol consumption and developing alcohol dependence revealed overrepresentation of the C allele of the 861G > C polymorphism of 5HT1B in alcoholics with inactive ALDH2, compared with its frequency in nonalcoholic controls. No significant differences in 5HT1B genotype and allele distributions were observed between alcoholics with active ALDH2 and controls, however. Taken together with recent observations, these results suggest that genetic variability of the 5HT1B receptor is involved in the development of some type of alcohol dependence.