Abnormal epithelial repair to damage participates in airway remodeling in asthma by the paracrine regulation of mesenchymal cell functions. Retinoids control epithelial functions through nuclear retinoic acid receptor (RAR) and retinoid X receptor (RXR) activation, yet their expression and contribution to epithelial repair and to airway remodeling in asthma are unknown. We determined the plasma levels of retinol and the immunohistochemical expression of retinoid receptors in damaged and repaired bronchial epithelium from 9 controls, 10 intermittent, 8 mild-to-moderate and 8 severe asthmatics. In addition, the effect of the retinoid receptor ligands, all-trans-retinoic acid, and 9-cis retinoic acid, on the synthesis of 38 factors potentially involved in epithelial repair and in airway remodeling was determined in human cultured airway epithelial cells and correlated with cell migration and proliferation. Circulating retinol was similar in the three patient groups. In contrast, the epithelial expression of RAR, RXR and RXR was greater in severe asthmatics, as compared to patients with milder disease and to controls. Retinoid receptor expression correlated positively with the proportion of morphologically intact epithelium. In vitro, retinoids upregulated the expression of the transcripts encoding TGF-1, metalloproteinase-9, 1-integrin, and hepatocyte growth factor receptor and promoted wound repair and chemokinesis of human airway epithelial cells without altering proliferation. Cell treatment with an anti-TGF-1 mAb partially reduced retinoid-induced effects. Persistent interaction between retinoids and some of their receptors, which are overexpressed by the bronchial epithelium of severe asthmatics, may contribute to an abnormal repair and to airway remodeling, partly through TGF-1 production.