RATIONALE: Changes in airway epithelial cell differentiation, driven in part by interleukin-13 (IL-13), are important in asthma. Micro-RNAs (miRNAs) regulate cell differentiation in many systems and could contribute to epithelial abnormalities in asthma. OBJECTIVES: Determine whether airway epithelial miRNA expression is altered in asthma and identify IL-13-regulated miRNAs. METHODS: We used miRNA microarrays to analyze bronchial epithelial brushings from 16 "steroid-naïve" asthmatics before and after inhaled corticosteroids, 19 "steroid-using" asthmatics and 12 healthy controls and the effects of IL-13 and corticosteroids on cultured bronchial epithelial cells. We used quantitative PCR to confirm selected microarray results. MEASUREMENTS AND MAIN RESULTS: Most (12/16) "steroid-naïve" asthmatics had a markedly abnormal pattern of bronchial epithelial miRNA expression by microarray analysis. Compared with controls, 217 miRNAs were differentially expressed in "steroid-naïve" asthma and 200 in "steroid-using" asthma (FDR<0.05). Treatment with inhaled corticosteroids had modest effects on miRNA expression in "steroid-naïve" asthma, inducing a statistically significant (FDR<0.05) change for only 9 miRNAs. qPCR analysis confirmed differential expression of 22 miRNAs that were highly differentially expressed by microarrays. IL-13 stimulation recapitulated changes in many differentially expressed miRNAs, including four members of the miR-34/449 family, and these changes in miR-34/449 family members were resistant to corticosteroids. CONCLUSIONS: Dramatic alterations of airway epithelial cell miRNA levels are a common feature of asthma. These alterations are only modestly corrected by inhaled corticosteroids. IL-13 effects may account for some of these alterations, including repression of miR-34/449 family members that have established roles in airway epithelial cell differentiation.