We present here the clinical course of 4 children with cystic fibrosis, deltaF508/deltaF508, who were admitted with severe respiratory distress and in whom no improvement was obtained by intensive antibiotic therapy and systemic corticosteroids. Chest computed-tomography scans showed hyperinflation and atelectasis. The severity of these exacerbations was explained neither by visible mucus plugging nor by allergic bronchopulmonary aspergillosis. We hypothesized that these clinical features were related to a severe inflammatory process in small airways. Therefore, a high-dose short course of methylprednisolone (1 g/1.73 m(2) per day for 3 days) was given; all the patients' conditions were dramatically improved, and the therapy was safe. To our knowledge, this is the first reported use of bolus methylprednisolone in the treatment of uncontrolled pulmonary exacerbation in children with cystic fibrosis.