OBJECTIVE: To determine the benefit of nasally inhaled dornase alfa in cystic fibrosis (CF) sinusitis. DESIGN: Retrospective chart review comparing postsurgical course, radiographic studies, and pulmonary function test results in patients who were treated with nasally inhaled dornase alfa with those in patients who were not treated with dornase alfa. PATIENTS: Twenty consecutive patients with CF who underwent functional endoscopic sinus surgery from 1993 to 1997 were included in the study. Treatment with nasally inhaled dornase alfa was initiated in 5 of the 20 patients after they underwent functional endoscopic sinus surgery. SETTING: Tertiary care academic center. RESULTS: The dornase alfa-treated patients had less mucosal edema and no polyps at serial endoscopy over 3 years compared with the non-dornase alfa-treated patients. The patients who received nasally inhaled dornase alfa also underwent fewer revision functional endoscopic sinus surgical procedures (1.6 vs 3.2), even though there was essentially no change in pulmonary function test results in these patients. CONCLUSIONS: Sinusitis continues to be a major cause of morbidity in patients with CF. Symptomatic patients frequently require multiple drug regimens, including long-term systemic antibiotic therapy, topical and systemic steroid therapy, and antibiotic nasal irrigations. This preliminary study indicates the potential impact of nasally inhaled dornase alfa in controlling postoperative symptoms in CF sinusitis.