Salbutamol is a widely used drug among elite athletes. We wanted to provide more information on the effects of salbutamol in nonasthmatic athletes. Seventeen highly conditioned male athletes (Vo2max > 70 ml · kg−1· min−1) participated in a randomized, double-blind and placebo-controlled cross-over study. Nebulized salbutamol (0.05 mg/kg) or placebo was inhaled prior to a high intensity (110% of Vo2max) treadmill run to exhaustion. The measured variables included endurance time, oxygen uptake, ventilation, breathing rate, heart rate, and oxygen saturation. Lung function was measured as forced expiratory volume in the first second (FEV1) before and after medication, and during the recovery from the run. The high intensity runs led to total exhaustion after 4–10 min. A close-to-significant shortening in endurance time was found when salbutamol was given. During the running (0–4 min) the oxygen uptake was slightly lower and the heart rate was slightly higher when salbutamol was given. No differences were found in peak oxygen uptake, peak heart rate, ventilation, breathing rate or oxygen saturation. FEV1 reflected an increase in airway caliber after the inhalation of salbutamol. These changes were still present in the recovery from the test run with the exception of the measurement immediately after the exercise. Although evidence for β-adrenergic stimulation was found, it was concluded that a therapeutic dose of nebulized salbutamol does not improve performance in highly trained athletes during a high-intensity run to exhaustion.