Airway inflammation and infection are present in patients with mild lung disease in cystic fibrosis (CF), suggesting the need for early treatment. In a previously reported large multicenter trial, dornase alfa improved pulmonary function and decreased the need for hospitalization in patients with CF over 5 years of age and with forced vital capacity greater than 40% predicted. We report here preliminary results of a study of dornase alfa delivered by two different nebulizer systems to patients with mild lung disease in CF and near normal lung function. Even in this mild group dornase alfa improved pulmonary function. The delivery system with the smaller droplet size tended to provide greater improvement than the system with the larger droplet size, although this difference was not satisfactorily significant. We have reviewed characteristics of nebulizers and patients' lung function that might affect efficacy of different nebulizer delivery systems. Our results indicate that treatment can improve pulmonary function in patients with mild lung disease in CF and illustrate the need for further studies in this group of patients.