Circulating epinephrine plays an important role in skeletal muscle vasodilation during mental stress. Normotensive adults homozygous for glycine (Gly) of the Arg16/Gly beta2-adrenergic receptor polymorphism have a greater forearm beta2-receptor mediated vasodilation and a higher cardiac output response to isometric handgrip than arginine (Arg) homozygotes. To test the hypothesis that the Arg16/Gly beta2-adrenergic receptor polymorphism affects the forearm blood flow (FBF) and hemodynamic response to mental stress, and whether venous catecholamine concentrations predicted these responses, we measured venous epinephrine, norepinephrine, heart rate (HR), arterial pressure (Finapres), and FBF during mental stress in healthy subjects homozygous for Gly16 (n = 30; mean age +/- SE: 30 +/- 1.2, 13 women) and Arg16 (n = 17, age 30 +/- 1.6, 11 women). Resting HR, blood pressure, and FBF responses to mental stress were similar between genotype groups. There were positive correlations between epinephrine and peak FBF (r = 0.694, P < 0.001), peak forearm vascular conductance (r = 0.677, P < 0.001) and the change in epinephrine to the change in HR (r = 0.456, P = 0.002) in all subjects. These correlations were not significantly different in the Gly16 and Arg16 groups. We conclude that venous epinephrine predicts the FBF response to mental stress, and the increase in epinephrine is also correlated with the increase in HR. Furthermore, the Arg16/Gly beta2-receptor polymorphism has no significant influence on the FBF or cardiovascular responses to mental stress.