The increased longevity of patients with cystic fibrosis has resulted in a concomitant increase in the frequency with which pneumothorax is seen. While several approaches to this problem have been available from both a medical and surgical standpoint, unsettled questions remain regarding the efficacy of various modalities of therapy. A review of our own experience with 170 episodes of pneumothorax has provided a basis for proposing what appears to be a reasoned approach to therapy. During the past 12 years, 65 patients ages 5 to 32 years experienced 170 episodes of pneumothorax. Of the 211 trials of treatment, all yielded a high rate of initial resolution (70% to 100%) but rates of recurrence were high. The recurrence rates were: observation 60%, thoracentesis 79%, trochar thoracotomy 63%, tetracycline sclerosis 86%, and silver nitrate 43%. Quinacrine sclerosis yielded an acceptable recurrence rate of 12.5% and partial pleurectomy had no recurrence. There was no statistical difference in the pulmonary function parameters determined before pneumothorax and after chemical pleurodesis or partial pleurectomy. Based upon the data obtained in this review, we recommend that initial management of the pneumothorax include evacuation of the pneumothorax using a chest tube and then chemical pleurodesis using quinacrine sclerosis. In those cases where this pleurodesis fails, upper-partial pleurectomy with obliteration of pleural blebs via a limited thoracentesis is the treatment of choice. An occasional patient requires a concomitant lobectomy.