We compared standard chest physical therapy and postural drainage (CPT/PD) with a new airway clearance therapy called high-frequency chest wall oscillation (HFCWO) in a group of stable cystic fibrosis (CF) patients. In this crossover trial, 29 CF patients (15 males, 14 females), aged 7-47 years that met the inclusion criteria were randomly assigned to alternate CPT/PD and HFCWO, on a daily basis, over a 4 day period. Each patient received 2 days of each form of therapy; treatment frequency and the length of treatment were the same for both techniques. Expectorated secretions were collected during each 30 minute therapy session and for 15 minutes following treatment. The wet and dry weights of collected secretions were determined gravimetrically, and the therapy methods were compared. Significantly more sputum was expectorated during HFCWO than during CPT/PD as determined by both the wet (P < 0.001) and the dry (P < 0.01) measurements. This study suggests that HFCWO is at least as effective as manual CPT/PD in clearing secretions from the airways in patients with cystic fibrosis.