The optimal duration of therapy for acute exacerbations of cystic fibrosis (CF) has not been defined, and the utility of serial pulmonary function testing in predicting the duration of therapy has yet to be established. In a review of 90 pulmonary exacerbations of 39 patients with CF requiring hospitalization, we found that 72% of the patients recovered following 2 weeks of intravenous antibiotics and aggressive chest physiotherapy, and that 28% required an extended third week of therapy. Recovery was delayed in patients with more severe chronic pulmonary disease, but the rate of improvement was independent of the degree of pulmonary deterioration with the acute exacerbation. A 40% recovery of FEV1 at 1 week was found to correlate significantly with the duration of hospitalization in the 90 patients. When prospectively applied to a second series of consecutively hospitalized patients with CF, 25/28 patients admitted for 2 weeks demonstrated > 40% improvement in FEV1 at 1 week, as compared to 5/10 patients subsequently treated for > or = 3 weeks (P = 0.030). The predictive values for 2- or 3-week hospitalizations with 1-week interval recovery of > 40% or < or = 40% in FEV1 were 79% and 62%, respectively. These findings suggest that the response to intensive therapy in CF exacerbations is variable and that improvements in pulmonary function after 1 week of therapy may be used to predict the subsequent duration of therapy in the majority of CF patients with pulmonary exacerbations.