In a recent study, the difference between asthma and eosinophilic bronchitis (a condition characterized by cough but not airway hyperresponsiveness or airflow obstruction) was infiltration of airway smooth muscle (ASM) by mast cells. Mast cells produce a variety of lipid mediators, chemokines, cytokines, and enzymes that may interact with ASM cells to cause hyperreactivity to constrictive stimuli and proliferation, and activated ASM can produce stem cell factor and other chemokines, cytokines, and growth factors that may act in recruitment, differentiation, and retention of mast cells. Mast cell infiltration of the airways in asthma is T-cell–dependent, and TH2 cytokines from T cells and other sources act in mast cell expansion from circulating and tissue precursors. The recent data on interactions of mast cells and ASM suggest that this could be an important contributor to airway hyperresponsiveness in asthma. Why this occurs in asthma and how it is sustained remain to be established.