The beta-2 adrenergic receptors (2AR) play an important role in lung fluid regulation. Previous research has suggested that subjects homozygous for Arginine at amino acid 16 of the 2AR (Arg16) may have attenuated receptor function relative to subjects homozygous for Glycine at the same amino acid (Gly16). We sought to determine if the Arg16Gly polymorphism of the 2AR influenced lung fluid balance in response to rapid saline infusion. We hypothesized that subjects homozygous for Arg at amino acid 16 (n=14) would have greater lung fluid accumulation compared to those homozygous for Gly (n=15) following a rapid intravenous infusion of isotonic saline (30mls/kg over 17 minutes). Changes in lung fluid were determined using measures of lung density and tissue volume (CT imaging) and measures of pulmonary capillary blood volume (Vc) and alveolar-capillary conductance (DM, determined from the simultaneous assessment of the diffusing capacities of the lungs for carbon monoxide and nitric oxide). The saline infusion resulted in elevated catecholamines in both genotype groups (Arg16= 283±117% vs. Gly16= 252±118%, p>0.05). The Arg16 group had a larger decrease in DM and increase in lung tissue volume and lung water post saline infusion relative to the Gly16 group (DM -13±14 vs 0±26%, p<0.05, lung tissue volume=13±11 vs 3±11%, lung water +90±66 vs +48±144ml, p=0.10, p<0.05, for Arg vs. Gly16, respectively, mean±SD). These data suggest that subjects homozygous for Arg at amino acid 16 of the 2AR have a greater susceptibility for lung fluid accumulation relative to subjects homozygous for Gly at this position.