As patients with cystic fibrosis live longer, spontaneous pneumothoraces are seen with increasing frequency. Severe underlying pulmonary disease in these patients makes them particularly susceptible to life-threatening respiratory distress. Several modalities, including chemical sclerosis and open thoracotomy with pleurectomy, have been used to treat pneumothoraces in these patients. In the past 4 years, pneumothoraces in five patients (ages 9-22 years) with cystic fibrosis have been treated with thoracoscopy and talc poudrage. All procedures were performed under either regional or general anesthesia, depending on the age of the patient. Thoracoscopy was performed with a rod lens system and a 5.5-mm trocar, using biopsy forceps to lyse pleural adhesions, all of which ensures access to the entire pleural surface. United States Pharmacopeia-certified talc was insufflated to cover the entire pleural surface. There were no complications, and the patients had minimal pleural pain. Follow-up ranged from 6 months to 4 years. No patient has had a recurrent pneumothorax on the treated side. Thoracoscopy with talc poudrage is a preferable alternative to chemical sclerosis or thoracotomy for treating pneumothoraces in patients with cystic fibrosis. The procedure may be performed under regional anesthesia and allows rapid and complete sclerosis of the pleural cavity.