By cleaving neutrophil-derived DNA present in the infected lungs of patients with cystic fibrosis (CF), dornase alfa (recombinant human deoxyribonuclease I) reduces the adhesiveness and viscoelasticity of CF sputum. Well designed clinical studies performed in patients with CF and mild to moderate pulmonary disease [forced vital capacity (FVC) > or = 40% of predicted value] show that aerosolised dornase alfa improves lung function, achieving a 6 to 7% increase from baseline in forced expiratory volume in 1 second (FEV1) after 6 months' therapy. Improvements in general well-being and CF-related symptoms were also noted by patients. Importantly, dornase alfa reduced the relative risk of respiratory exacerbations requiring parenteral antibiotics by 22 to 34% compared with placebo. Short term studies with dornase alfa in patients with more severe pulmonary disease (FVC < 40% of predicted value) and in those with acute infectious exacerbations did not reveal any significant improvements in pulmonary function, although long term studies are required to fully determine efficacy. Voice alteration, laryngitis or rash may develop with dornase alfa therapy, although more clinical experience with the agent is required to define its tolerability profile. Anaphylaxis has not been reported with dornase alfa to date. In summary, aerosolised dornase alfa offers modest improvements in lung function and, importantly, a reduced risk of respiratory exacerbations in patients with CF and an FVC > or = 40% of the predicted value, thus representing an important adjunct agent in this patient group.