Neuroimaging has consistently documented reductions in the brain tissue of alcoholics. Inability to control comorbidity, environmental insult, and nutritional deficiency, however, confound the ability to assess whether ethanol itself is neurotoxic. Here we report monkey oral ethanol self-administration combined with MR imaging to characterize brain changes over 15 months in 18 well-nourished rhesus macaques. Significant brain volume shrinkage occurred in the cerebral cortices of monkeys drinking ≥ 3 g/kg ethanol/day (12 alcoholic drinks) at 6 months, and this persisted throughout the period of continuous access to ethanol. Correlation analyses revealed a cerebral cortical volumetric loss of ~0.11% of the intracranial vault for each daily drink (0.25 g/kg), and selective vulnerability of cortical and non-cortical brain regions. These results demonstrate for the first time a direct relation between oral ethanol intake and measures of decreased brain gray matter volume in vivo in primates. Notably, greater volume shrinkage occurred in monkeys with younger drinking onset that ultimately became heavier drinkers than monkeys with older drinking onset. The pattern of volumetric changes observed in nonhuman primates following 15 months of drinking suggests that cerebral cortical gray matter changes are the first macroscopic manifestation of chronic ethanol exposure in the brain.