Nebulized epinephrine has been advocated as a treatment for airway obstruction in infants with bronchiolitis; however, its effect on respiratory mechanics and gas exchange has been poorly documented to date. We performed a preinterventional and postinterventional study with primary outcome measures of mechanics (measured by single-breath occlusion passive deflation) and oxygenation and ventilation indices in order to measure the effects of nebulized epinephrine in infants requiring mechanical ventilation for RSV-positive bronchiolitis. A two-compartment model was used to describe respiratory mechanics in patients with nonlinear flow-volume curves. Nebulized epinephrine (0.5 mg/kg) was administered to 15 patients (median age, 0.19 yr; weight, 4.4 kg). Resistance decreased significantly in slow and fast compartments in 87 and 70% of patients, respectively. Median resistance in the slow compartment decreased from 0.427 to 0.198 cm H2O/ml/s (p = 0.0015) and in the fast compartment from 0.167 to 0.116 cm H2O/ ml/s (p = 0.018). Compliance, oxygenation index, and ventilation index were not significantly changed after administration of epinephrine. We conclude that nebulized epinephrine substantially improves respiratory system resistance but not oxygenation or ventilation indices. This may be because of the effects of epinephrine on oxygen consumption or ventilation-perfusion matching.