Background The Gly16 β₂-adrenergic receptor (β₂AR) polymorphism is a common variant of the β₂AR that displays depressed function caused by enhanced receptor downregulation in vitro compared with the Arg16 receptor. Methods and results We studied 20 healthy, normotensive, nonsmoking white individuals who were homozygous for either the Arg16 (n = 10) or the Gly16 (n = 10) genotype. Plethysmographic lower-limb blood flow, blood pressure, and 2-dimensional echocardiograms were recorded at baseline and after 15-minute incremental infusions of terbutaline (100 to 300 ng/kg per minute). Baseline heart rates, blood pressures, and flows were similar in both groups, but at the maximum dose of terbutaline, limb blood flow was less (P < .05), calculated vascular resistance was greater (P < .05), and systolic and diastolic blood pressures were greater in patients with Gly16 than in those with Arg16 (both P < .05). In contrast, terbutaline-stimulated heart rates were not different. In a separate group of 20 homozygous individuals (12 Arg16, 8 Gly16), there were no differences in 2-dimensional echocardiographically determined ventricular function. Conclusions We conclude that the Gly16 β₂AR polymorphism imparts attenuated vasodilatory responses to catecholamines in normal human beings and is an important genetic component in the regulation of peripheral blood flow and systemic arterial pressure.