African American (AA) males have the lowest life expectancy and highest death rate compared to all other racial-gender groups, including AA females. Most striking is that hypertensive AA males are 3-14 times more likely to have kidney disease compared to other hypertensive groups. The reason for this striking disparity remains unknown. What is known is that racism can be a significant contributor to disease risk in AAs. Our preliminary results reveal that while both AA male and female experience racism only AA males show activation of the hypothalamus-pituitary-adrenal axis and associated increased biomarkers of renal injury. These findings raise the questions: why do AA males’ experiences of racism result in activation of the hypothalamus-pituitary-adrenal axis (HPA) system and how are AA males and females different in their biological response to perceived racism (PR). This project proposes to investigate these important questions. The stress process and men’s health disparity models suggest that maladaptive coping and low social resources contribute to disease risk perhaps by promoting the activation of the HPA system. Anger and hostility are coping methods that AA males often employ in dealing with racist and unjust experiences while social support is often employed by women. Therefore, in males exposed to racism and stress the HPA is activated resulting in increased ALDO and cortisol and sympathetic nerve output; both of which promote cardio renal diseases. ALDO is known to: be elevated in kidney disease; be higher in AAs; and promote kidney injury in the setting of salt-sensitive hypertension by activating the mineralocorticoid receptor (MR) resulting in subsequent inflammation and fibrosis development through RAC 1 pathway signaling. However, in females the HPA is not activated due to the use of social support. Thus, ALDO is a stress hormone that likely plays a major role in the kidney disease disparity in this vulnerable group of AA males.