Exogenous surfactant treatment inhibits antigen-induced airway obstruction in sensitized guinea-pigs. Aerosolized surfactant also improves respiratory function in asthmatic patients. The aim of the present study was to determine whether aerosolized surfactant inhibits nonallergic airway obstruction induced by acetylcholine. Anaesthetized Wistar rats were treated by aerosol with the beta2-adrenoceptor agonist terbutaline, surfactant (Alveofact), a surfactant-terbutaline combination, or vehicle (control). Animals were then challenged by aerosolized acetylcholine to elicit receptor-mediated airway obstruction. A second group of animals was challenged with intravenous acetylcholine. Respiratory function variables were measured by body plethysmography before and after treatment, and after the acetylcholine challenge. Baseline lung function values before and after treatment were similar in all groups. Acetylcholine challenge by aerosol increased lung resistance by 64% in control animals. Pretreatment with terbutaline and surfactant significantly limited the increase of lung resistance to +36 and +34%, respectively. Simultaneous aerosolization of surfactant and terbutaline also inhibited airway obstruction but their effects were not additive. By contrast, terbutaline treatment inhibited the effects of intravenous acetylcholine, but surfactant did not. In conclusion, we suggest that surfactant aerosol may prevent acetylcholine and other pharmacological agents from reaching the airway smooth muscle from the airway lumen but not via the bloodstream.