OBJECTIVE --We attempted to replicate a positive allelic association between the A1 allele of DRD2 (the D2 dopamine receptor locus) and alcoholism that has been reported. METHODS --We compared allele frequencies at the previously described Taq I restriction fragment length polymorphism system of DRD2 in alcoholics and random population controls. METHODS --The alcoholic subjects were 44 unrelated white individuals, diagnosed by direct structured interview to have alcohol dependence (by the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition, criteria). The subjects in our random population control group (N = 68) were also white. RESULTS --For the control group, allele frequencies at DRD2 were 0.20 (A1) and 0.80 (A2). For the alcoholic group overall, allele frequencies were 0.23 (A1) and 0.77 (A2). There were no significant differences in allele frequencies at the DRD2 locus between alcoholics and controls. The allele frequencies in both groups agreed closely with those observed in most previously described control populations. Subtyping the alcoholic group according to presence or absence of family history of alcoholism, presence or absence of antisocial personality disorder, age of onset, presence or absence of physical withdrawal symptoms, or recent alcohol consumption (as a measure of severity) did not in any case reveal significant differences in allele frequencies. CONCLUSIONS --We were not able to replicate the results previously reported. We conclude that our data do not support an allelic association between the A1 allele at DRD2 and alcoholism.