Infiltration of the airways by T helper type 2 (Th2) lymphocytes is a well-recognized feature of bronchial asthma. Monocyte-derived chemokine (MDC) is a potent attractant which activates Th2 lymphocytes via the chemokine receptor CCR4. We have investigated both leukocyte recruitment and MDC release into the airways of asthmatic patients. Differential cell counts in bronchoalveolar lavage (BAL) fluid showed that numbers of lymphocytes and eosinophils were elevated in asthmatics compared with normal subjects (median, 6.1 vs. 1.0 x 10(3)/ml, P < 0.005 and 1.4 vs. 0.24 x 10(3)/ml, P = 0.001, respectively). By enzyme-linked immunosorbent assay it was demonstrated that MDC concentrations were significantly elevated in BAL fluid from asthmatics compared with normals (medians 282 pg/ml, range 190-780 pg/ml vs. median 29 pg/ml range 17-82 pg/ml, P < 0.001). Interestingly, there was a significant correlation between MDC levels and the bronchoconstrictive response to methacholine [PC20 forced expiratory volume (FEV)1, r = -0.78, P = 0.001], suggesting that MDC may be involved in the severity of the disease. By immunohistochemistry, MDC was localized predominantly to the bronchial epithelium in bronchial biopsies derived from stable asthmatics. Moreover, primary human airway epithelial cells were found to release MDC upon cytokine stimulation. These findings suggest that MDC may play a major role in the pathogenesis of bronchial asthma.