In situ hybridization and immunohistochemical analyses of lung tissue revealed the in vivo expression of CAMs in ASM.5–6 Specifically, after lipopolysaccharide (LPS) stimulation of rat lungs, ASM markedly enhanced ICAM-1 expression both at the protein and messenger RNA levels.5Using in vivo human bronchial tissue transplanted onto the flank of severe combined immunodeficiency (or SCID) mice, Lazaar and colleagues6 demonstrated a marked increase in ICAM-1 and vascular CAM (VCAM)-1 expression after the injection of tumor necrosis factor (TNF)-α, a cytokine that is produced in considerable quantities in asthmatic airways,7 into the bronchial lumen of the grafted tissue. Further in vitro studies confirmed the expression of ICAM-1 and VCAM-1 on cultured ASM that was inducible by a wide range of inflammatory mediators such as TNF-α, interleukin (IL)-1β, or interferon (IFN)-γ.,6,8 Although the function of CAMs in ASM remains incompletely defined, investigators6,9–11 have clearly demonstrated that the surface expression of CAMs in ASM may be pivotal in regulating ASM cell interactions with a variety of inflammatory cells relevant for the pathogenesis of asthma. Studies6 have suggested that activated T cells avidly adhere to cultured ASM, an interaction that is mediated through ICAM-1, VCAM-1, and CD44 cells. The latter interaction enhances T-cell binding that increases bronchoconstrictor responses to acetylcholine and impairs relaxation responses to isoproterenol.9 More recently, investigators12 demonstrated that CD4+ T cells interact with ASM in vivo. Using adoptive transfer of CD4+ T cells from sensitized rats, there is a marked increase in the proliferation and inhibition of apoptosis of airway myocytes in naïve recipients on repeated allergen challenge. The consequence of the enhanced proliferation in ASM in vivo is an increase in ASM mass and airway hyperresponsiveness. Additionally, genetically modified CD4+ T cells expressing enhanced green fluorescent protein were localized by confocal microscopy to be juxtaposed to the ASM. This finding is clinically relevant and implies that CD4+ T cells may directly modulate ASM function through cell-cell interactions in vivo.,12 Furthermore, other inflammatory cells including eosinophils10and recently neutrophils11 also adhere to ASM in vitro. The attachment of such cells to ASM was inhibited by the presence of anti-ICAM-1 and VCAM-1 antibodies. Further, important studies,13 showing mast cell-ASM interactions in vivo in subjects with asthma clearly have demonstrated that cell-cell attachment may modulate and alter stromal cell function. Collectively, these studies have suggested that direct interactions among leukocytes, inflammatory cells, and ASM via CAMs can directly contribute to the pathogenesis of asthma and, as such, therapeutic targets that will disrupt cell-cell adherence may provide new approaches to bronchodilatation while inhibiting the perpetuation of airway inflammation in the submucosa.