Although moderate alcohol consumption has been associated with a lower risk of cardiovascular disease, underlying physiologic mechanisms are not fully understood. Data relating alcohol intake to atrial natriuretic peptide (ANP) have been inconsistent. We evaluated whether alcohol consumption was associated with plasma ANP in 1,345 participants from the Hypertension Genetic Epidemiology Network (HyperGEN) study. We used random effect models to estimate the adjusted means of logarithmic transformed ANP. The mean age was 35.8 +/- 8.6 years, 91% were normotensive, 46% were men, and 40% and 60% were African-Americans and whites, respectively. In a model adjusting for age, body mass index, field center, education, gender, race, and serum albumin, alcohol consumption was positively associated with ANP in men (p < 0.0001 for trend) and women (p = 0.0014) and in African-Americans (p = 0.006) and whites (p < 0.0001). The adjusted mean of log-transformed ANP was 3.68, 3.67, 3.77, 3.76, 3.86, and 3.91 pg/ml in lifetime abstainers, former drinkers, and current drinkers of 1 to 6, 7 to 12, 13 to 24, and > 24 g/d, respectively. Controlling for additional factors, including left atrial size, ejection fraction, left ventricular mass, end-diastolic volume, systolic blood pressure, smoking, lipids, and serum creatinine did not change the results. Restriction to normotensive subjects yielded similar results. Alcohol intake was associated positively with systolic and diastolic blood pressure (p < 0.0001 each for trend). In conclusion, our data have shown a positive and linear association between alcohol consumption and ANP in men and women, irrespective of race.