INTRODUCTION: No evidence based treatment is available for atelectasis. We aimed to evaluate the clinical and radiologic changes in pediatric patients who received DNase for persistent atelectasis that could not be attributed to cardiovascular causes, and who were unresponsive to treatment with inhaled bronchodilators and physiotherapy. METHODS: All non-cystic fibrosis pediatric patients who received nebulised or endotracheally instilled DNase for atelectasis between 1998 and 2002, with and without mechanical ventilation, were analysed in a retrospective descriptive study. The endpoints were the blood pCO2, the heart rate, the respiratory rate, the FiO2 and the chest X-ray scores before and after treatment. RESULTS: In 25 of 30 patients (median [range] age, 1.6 [0.1-11] years) who met inclusion criteria, paired data of at least three endpoints were available. All clinical parameters improved significantly within 2 hours (P < 0.01), except for the heart rate (P = 0.06). Chest X-ray scores improved significantly within 24 hours after DNase treatment (P < 0.001). Individual improvement was observed in 17 patients and no clinical change was observed in five patients. Temporary deterioration (n = 3) was associated with increased airway obstruction and desaturations. No other complications were observed. CONCLUSION: After treatment with DNase for atelectasis of presumably infectious origin in non-cystic fibrosis pediatric patients, rapid clinical improvement was observed within 2 hours and radiologic improvement was documented within 24 hours in the large majority of children, and increased airway obstruction and ventilation-perfusion mismatch occurred in three children, possibly due to rapid mobilisation of mucus. DNase may be an effective treatment for infectious atelectasis in non-cystic fibrosis pediatric patients.