Current treatments of lung diseases involving mucus hypersecretion include strategies to change the physical properties of pulmonary secretions to improve lung clearance. This can be achieved by various therapeutic approaches, either physical, e.g. high frequency chest compression (HFCC), or biochemical, e.g. DNase. To illustrate the possibilities of combining physical and chemical treatments, we evaluated the effects of combinations of oscillation and DNasein vitro on spinnability of cystic fibrosis (CF) sputum, measured with a filancemeter.Aliquots of sputum from eight CF patients were subjected to the following protocols: (1) incubation with DNase in normal saline (10% dilution) for 15 min at 37° C to achieve 5 μg/ml final conc.; (2) airflow oscillation at 27 Hz similar to the airflow magnitude produced by a commercial HFCC device (3) negative control with no treatment; (4) positive (dilution) control, incubating with 10% saline by volume; (5) combination of DNase and oscillation; (6) combination of saline and oscillation. Treatment with DNase decreased spinnability significantly more than either saline or oscillation for 15 minutes, and more than saline after 30 minutes. Oscillation of CF sputum over 15 and 30 minutes decreased spinnability significantly with respect to its control. The combination of DNase and oscillation decreased spinnability significantly more than treatment with DNase alone (p<0.01).These changes are considered potentially beneficial for CF patients, although the relationship between spinnability and clinical outcomes has not yet been determined. These in vitro results demonstrate a maximal effect from combining DNase and oscillation, and suggest potential superiority of combinations of biochemical and physical treatments for CF patients. Other combination approaches, such as DNase and gelsolin, are currently being investigated.