Objective: To determine the effect of low-dose propranolol on maximal exercise capacity in patients with postural tachycardia syndrome (POTS). Methods: We compared the effect of placebo vs a single low dose of propranolol (20 mg) on peak oxygen consumption (VO(2)max), an established measure of exercise capacity, in 11 patients with POTS and 7 healthy subjects in a randomized, double-blind study. Subjects exercised on a semirecumbent bicycle, with increasing intervals of resistance to maximal effort. Results: Maximal exercise capacity was similar between groups following placebo. Low-dose propranolol improved VO(2)max in patients with POTS (24.5 +/- 0.7 placebo vs 27.6 +/- 1.0 mL/min/kg propranolol; p = 0.024), but not healthy subjects. The increase in VO(2)max in POTS was associated with attenuated peak heart rate responses (142 +/- 8 propranolol vs 165 +/- 4 bpm placebo; p = 0.005) and improved stroke volume (81 +/- 4 propranolol vs 67 +/- 3 mL placebo; p = 0.013). In a separate cohort of POTS patients, neither high-dose propranolol (80 mg) nor metoprolol (100 mg) improved VO(2)max, despite similar lowering of heart rate. Conclusions: These findings suggest that nonselective beta-blockade with propranolol, when used at the low doses frequently used for treatment of POTS, may provide a modest beneficial effect to improve heart rate control and exercise capacity. Classification of evidence: This study provides Class II evidence that a single low dose of propranolol (20 mg) as compared with placebo is useful in increasing maximum exercise capacity measured 1 hour after medication. Neurology (R) 2013;80:1927-1933