Post-exercise hypotension (PEH) is widely observed in Caucasians (CA) and is associated with histamine receptors 1- and 2- (H1R and H2R) mediated post-exercise vasodilation. However, it appears that blacks (BL) may not exhibit PEH following aerobic exercise. Hence, this study sought to determine the extent to which BL develop PEH, and the contribution of histamine receptors to PEH (or lack thereof) in this population. Forty-nine (22 BL, 27 CA) young and healthy subjects completed the study. Subjects were randomly assigned to take either a combined H1R and H2R antagonist (fexofenadine and ranitidine) or a control placebo. Supine blood pressure (BP), cardiac output and peripheral vascular resistance measurements were obtained at baseline, as well as at 30 min, 60 min and 90 min after 45 min of treadmill exercise at 70% heart rate reserve. Exercise increased diastolic BP in young BL but not in CA. Post-exercise diastolic BP was also elevated in BL after exercise with histamine receptor blockade. Moreover, H1R and H2R blockade elicited differential responses in stroke volume between BL and CA at rest, and the difference remained following exercise. Our findings show differential BP responses following exercise in BL and CA, and a potential role of histamine receptors in mediating basal and post-exercise stroke volume in BL. The heightened BP and vascular responses to exercise stimulus is consistent with the greater CVD risk in BL.