There are now three small clinical trials16–1718 that have examined the effects of inhaled glutathione in patients with cystic fibrosis. Roum and colleagues16were first to report the use of inhaled glutathione (600 mg bid for 3 days, approximately 17 mg/kg/d) in seven patients with cystic fibrosis. The glutathione therapy was well tolerated and produced a twofold increase in epithelial lining fluid glutathione levels. In addition, these investigators found diminished superoxide production from BAL cells after glutathione therapy. One concern raised by these studies was the rapid rise in oxidized glutathione levels in the treated patients with cystic fibrosis. The percentage of oxidized glutathione in untreated patients with cystic fibrosis was 46%, and increased to 66% after treatment. This increase in oxidized glutathione can adversely change the redox status of the epithelial lining fluid, and may explain why Griese and colleagues17 failed to see a change in the oxidative state of the epithelial lining fluid proteins and lipids in their inhaled glutathione study. The study by Griese and colleagues17 used a highly efficient inhalation delivery system (86% of the emitted dose) to treat 17 patients with cystic fibrosis with two different regimens of glutathione (300 mg and 450 mg tid for 14 days, approximately 13 mg/kg/d and 20 mg/kg/d, respectively). Again, these regimens were well tolerated, increased epithelial lining fluid glutathione levels threefold to fourfold, and were associated with a significant improvement in the patient’s FEV1. However, a weakness of the two previous studies,16–17 is that neither were placebo controlled. The Bishop study is the first double-blind, placebo-controlled trial reported for inhaled glutathione in 19 patients with cystic fibrosis. The study by Bishop et al used a higher glutathione dosage (66 mg/kg/d, divided into four inhalations, for 8 weeks). This regimen was also well tolerated and associated with an improvement in peak flow over placebo group, along with a trend toward improvement in a number of other clinical indicators. Given the small size of the trial and the mild airway dysfunction in the cystic fibrosis population studied, these results are encouraging that inhaled glutathione therapy could be beneficial. In summary, inhaled glutathione therapy was well tolerated and efficacious in improving a variety of clinical indicators in all three studies16–1718 reported.