Interleukin-10 (IL-10) is a potent regulatory cytokine that decreases inflammatory responses and T-cell stimulation. We have found that respiratory epithelial lining fluid (ELF) from patients with cystic fibrosis (CF) contains significantly less soluble IL-10 than ELF of healthy control subjects. Although macrophages from the chronically infected lungs of CF patients appear to be one source of IL-10, little or no intracellular IL-10 was found in bronchoalveolar lavage macrophages from healthy control subjects, suggesting that there must be another source of this cytokine in healthy lungs. We found that bronchial epithelial cells from healthy control subjects constitutively produce IL-10, which appears to be downregulated in CF patients. It is thus likely that the bronchial epithelium plays an important role in regulating the local immune response, producing IL-10 to decrease inflammation in the healthy lung. Conversely, downregulation of epithelial IL-10 production in CF airways may contribute to enhancing local inflammation and tissue damage.