Health outcomes, including chronic disease and mortality, attributed to or associated with alcohol abuse are discrepant between African Americans and Whites. To date, the topic is not fully understood and few studies conducted have used biomarker indicators of health. We investigated whether the association between alcohol abuse and biomarkers of the neuroendocrine system vary between black or African American and White respondents aged 34-84 from the Midlife in the United States Study (MIDUS) II (2004-2006) (n=1129). Alcohol abuse was assessed with a modified version of the Michigan Alcohol Screening Test. Ordinary least squared (OLS) regression was used to evaluate whether race moderated the associations between alcohol abuse and four biomarkers-urinary cortisol and serum dehydroepiandrosterone sulfate (DHEA-S), epinephrine and norepinephrine-and two composite summary scores, each consisting of two components that characterize the hypothalamic pituitary adrenal (HPA)-axis and sympathetic nervous systems (SNS), respectively. Covariates included age, sex, education, income, current drinking, smoking, exercise, fast food consumption, heart disease, blood pressure, diabetes, body mass index, medication use, anxiety/depression, sleep duration, and cholesterol markers. Race significantly moderated the associations between alcohol abuse and norepinephrine concentration (χ [1]=4.48, p=0.034) and the SNS composite score (χ [1]=5.83, p=0.016). Alcohol abuse was associated with higher mean norepinephrine levels (b=0.26, standard error (SE)=0.12, p=0.034) and SNS composite score (b=0.23, SE=0.11, p=0.016) for African Americans compared to Whites. Interestingly, for Whites a paradoxical association between alcohol abuse, norepinephrine and SNS levels was observed; those who abused alcohol had lower mean norepinephrine levels than non-abusers. Race differences in neuroendocrine response could be biological pathways that contribute the excess risk of chronic disease and mortality attributed to alcohol abuse among African Americans compared to Whites. Replication of these analyses in larger cohorts are warranted in addition to further studies of underlying mechanisms among Blacks and Whites separately.