Diffuse paribronchiolitis (DPB) is a chronic progressive disease of the respiratory bronchioles, and has been improved by lowdose, long-term erythromycin (EMC) treatment. The therapeutic benefits may be derived from its anti-inflammatory and immunomodulatory properties rather than antimicrobial effect. However, there are few studies about the mechanism of immunomodulation by EMC treatment for patient with DPB. In this study, we quantified the changes of Th1 and Th2 cytokines in the bronchoalveolar lavage (BAL) fluid from patients with DPB after long term treatment with EMC. After the EMC treatment, a significant reduction in the number of lymphocytes was observed, and the CD4/CD8 ratio was elevated as well. The IL-2 and IFN-gamma levels in the BAL fluid were significantly decreased and the IL-4, IL-5, and IL-13 levels were significantly increased after EMC treatment. Our results suggest that the therapeutic benefits of long-term EMC treatment may be partially due to the immune system's shift from Th1 to Th2 cytokine production. (C) 2004 Elsevier Inc. All rights reserved.