The current model of lymphocyte extravasation into areas of inflammation involves the sequential engagement of multiple cell adhesion molecules (CAMs) expressed on lymphocytes and endothelial cells. In addition, the expression of CAMs and the elaboration of matrix by subendothelial/submucosal cells may contribute to the retention and stimulation of infiltrating cells in an inflammatory lesion. We previously demonstrated that mitogen-activated T cells adhered to airway smooth muscle (ASM) in an integrin-dependent fashion. ASM are MHC class II-negative and expressed low basal levels of intercellular adhesion molecule-1 (ICAM-1). In this study, we demonstrate that anti-CD3-stimulated peripheral blood T cells also adhere to ASM and markedly upregulate ICAM-1 expression and induce the expression of MHC class II on ASM. The induction of HLA-DR was completely inhibited, and the induction of ICAM-1 partially inhibited, by neutralizing antibody against interferon-gamma. Furthermore, in studies with bronchoalveolar lavage-derived T cells isolated from atopic donors following local antigen challenge, we observed adhesion to ASM and upregulation of ASM expression of ICAM-1 and HLA-DR similar to that seen with in vitro-activated T cells. Finally, we found that despite expression of ICAM-1 and HLA-DR, ASM could not present alloantigen to CD4+ T cells. These findings suggest that the interaction of activated T cells with parenchymal cells of the lung such as airway smooth muscle affects the phenotype of myocytes and thus may have significant implications for inflammatory diseases such as asthma or transplant rejection.