The specific aims of this study are to test the safety of aerosol administration of a cationic lipid:plasmid formulation 67A:pCF-1-CFTR in the lungs of cystic fibrosis patients and to assess the efficiency of transgene transfer in their lungs. A total of 8 patients receive a single dose of aerosolized lipid:plasmid formulation into the lungs, using a dose escalation strategy with the highest dose based on a trial in normal volunteers. Administration of the aerosol takes place in the hospital, and the subjects are monitored for at least two days in this setting. Safety is assesed by physical exams, High Resolution Computed Tomography, and/or chest radiography, pulmonary function tests, urinalysis, hematology and serum chemistry evaluations. Safety and efficiency of transgene transfer are assessed by bronchoscopy, bronchial brushings, and biopsies. To date, all eight patients have entered the study. Data concerning efficiency of gene transfer from our trial is still being evaluated. A companion study using the same lipid/DNA clinical test material and at the same dosages was performed at the Brampton Hospital in London. In the U.K. study, bioelectric correction of the CF defect was observed in some patients. A new clinical syndrome involving fevers and muscle aches has been discovered as a part of this study. Fevers to 104< and myalgias lasting 12-24 hours were observed in some (but not all) patients. The symptoms were well managed with Tylenol. We believe the syndrome may be due to CpG sequences present in the prokaryotic DNA used in the study. If this is confirmed, the findings will have broad significance to plasmid based gene transfer protocols being evaluated in the United States and abroad.