[3H]Naloxone binding was measured in frontal gray cortex, caudate nucleus, amygdala, hippocampus and cerebellar cortex obtained post mortem from human alcoholic and nonalcoholic subjects. Binding was found to be higher in alcoholics than in nonalcoholics for all of the brain regions examined, with a significant difference in the frontal cortex. When subjects were grouped by the presence or absence of the A1 (minor) allele of the D2 dopamine receptor gene, [3H]naloxone binding was lower in all brain regions examined of subjects with the A1 allele than in those without this allele, with a significant difference in the caudate nucleus. These findings suggest that one of the consequences of chronic alcohol exposure in humans is an enhancement of the brain opiate receptor system. However, the decreased [3H]naloxone binding observed in subjects with the A1 allele may be a compensatory response to their decreased dopaminergic modulation of opiate receptor activity.