The β2-adrenergic receptors (β2 ARs) play a role in renal Na+ regulation. Subjects homozygous for glycine at amino acid 16 (Gly16) of the β2AR have been shown to have enhanced β2-mediated vascular relaxation when compared to subjects homozygous for arginine (Arg16). However, Gly16 subjects have been shown to have higher blood pressure than Arg16 subjects. Given the dominant role of the kidneys in long-term blood pressure regulation, we sought to determine whether there were differences in renal Na+ handling between Gly16 (n=17) and Arg16 (n=14) subjects (Gly16: age, 30 ± 2 years; body mass index (BMI), 25 ± 11 kg m-2; Arg16: age, 30 ± 2 years; BMI, 25 ± 1 kg m-2). We measured urinary Na+ content before and for 3 h following rapid intravenous saline infusion (30 ml kg-1 in ∼16 min). Prior to the infusion, there were no differences in 24-h Na+ excretion between Gly16 and Arg16 subjects (Gly16, 183 ± 21 mmol; Arg16, 184 ± 20 mmol); however, systolic blood pressure (SBP) was significantly higher in Gly16 than Arg16 subjects with no differences observed in diastolic blood pressure (DBP) or mean arterial pressure (MAP) (SBP: Gly16, 117 ± 3 mmHg; Arg16, 109 ± 2 mmHg; DBP: Gly16, 78 ± 2 mmHg; Arg16, 77 ± 2 mmHg; MAP: Gly16, 90 ± 2 mmHg; Arg16, 89 ± 2 mmHg). With rapid saline infusion, MAP increased in both genotype groups (Gly16, 6.7% Arg16, 3.4%; P > 0.05). In the 3 h following Na+ infusion, Na+ excretion was less in Gly16 when compared to Arg16 subjects, with a trend towards significance when expressed as total Na+ excreted (Gly16, 66 ± 7 mmol; Arg16, 85 ± 9 mmol; P =0.07), and a significant difference when expressed as a fraction of the administered load (Gly16, 0.18 ± 0.02; Arg16, 0.28 ± 0.03; P < 0.01). These results suggest that the Arg16Gly polymorphism of the β2AR is associated with differences in natriuretic response to rapid saline infusion, which may influence long-term regulation of blood pressure.