Introduction: Human genetic studies have shown a greater risk of cardiometabolic disease with genetically lower natriuretic peptide (NP) levels. We have previously shown that blacks have lower NP levels than whites albeit in older individuals, which is partly explained by genetic factors. A high-carbohydrate challenge in young healthy whites was associated with a reduction in N-terminal pro atrial NP (NTproANP) levels, but no data exist in blacks. Hypothesis: We hypothesized that 1) the baseline differences in NP levels by race would be evident in young adults with no comorbidities; 2) blacks would have a reduction in NTproANP levels in response to high-carbohydrate challenge similar to whites but the magnitude of change would differ. Methods: Healthy self-identified blacks and whites were screened for the presence of laboratory abnormalities. Each eligible participant was provided 3 days of study diet to standardize salt intake. After the dietary intervention, subjects were brought to the clinical research unit for a high-carbohydrate challenge. Venous blood was collected every hour for 8 hours to perform biochemical assays. African ancestry proportions among self-identified blacks were also determined. Results: We recruited 56 healthy participants with a mean age of 26 years, 48% female, 54% whites, mean body mass index 26 kg/m 2 , and an average proportion of 90% African ancestry among self-identified blacks. We found that BNP levels were 24% (95% CI 53 to 6) and N-terminal-proB-type NP (NTproBNP) levels were 44% (95% CI 99 to 17) lower in blacks compared with whites. The decrease in NTproANP levels in response to carbohydrate challenge differed by race (p for interaction=0.03). In response to a carbohydrate challenge, blacks had a 24% reduction in the NTproANP levels (p=0.01) vs. a 47% decrease in the NTproANP in whites (p<0.001) ( Figure, Panel A ), with no change in NTproBNP levels in both races ( Figure, Panel B ). Conclusions: Blacks have an endogenously suppressed NP system which may be a biologic determinant contributing to racial disparities in cardiometabolic disease. We have shown that high-carbohydrate diet has a differential effect on NP system by race which needs to be considered while individualizing strategies for disease prevention. ( NCT# 03072602 ).