Infants with respiratory syncytial virus (RSV) bronchiolitis are deficient in surfactant, both in quantity and ability to reduce surface tension. New evidence suggests surfactant has a role in maintaining the patency of conducting airways, which has implications for RSV bronchiolitis. A randomized, controlled pilot study was undertaken to assess the effects of exogenous surfactant supplementation to RSV-positive infants on pulmonary mechanics, indices of gas exchange, and the phospholipid composition of bronchoalveolar lavage fluid (BALF). Nineteen ventilated infants (median corrected age 4 wk) received either two doses of surfactant (Survanta, 100 mg/kg) within 24 and 48 h of mechanical ventilation (n = 9), or air placebo (n = 10). Static lung compliance and resistance of infants in the placebo but not in the surfactant-treated group became progressively worse over the first 30 h following enrollment. Although no significant acute changes in gas exchange parameters were seen following surfactant, infants in the surfactant group showed a more rapid improvement in oxygenation and ventilation indices over the first 60 h of ventilation. Surfactant status was assessed from the concentration ratio in BALF of the disaturated phospholipid species dipalmitoylphosphatidylcholine to that of the monounsaturated species palmitoyloleoylphosphatidylcholine. This ratio correlated with both lung compliance (positively) and resistance (negatively), and over time increased in the treated group and declined in placebo infants. The data from this pilot study suggest that functional surfactant has a role in maintaining small airway patency as well as lung compliance in infants infected with RSV and an outcome study is now warranted.