Abstract Eosinophilia of lung and blood associated with injury to the mucociliary escalator and excessive shedding of bronchial epithelium are hallmarks of both allergic and nonallergic asthma. In vitro, the eosinophil granule major basic protein (MBP) is toxic to helminths and to mammalian cells, including human respiratory epithelium. The MBP-mediated damage to the respiratory epithelium consists of desquamation and frank destruction of ciliated cells. Increased sputum MBP concentration is a good marker for asthma, and patients treated for acute asthma have high levels of MBP in their sputa, which decrease after treatment. Peak sputum MBP levels approximate concentrations toxic to respiratory epithelium in vitro. In the lungs of patients who had died of asthma, MBP has been localized outside of the eosinophil in association with damage to the epithelium. Overall, these and other findings suggest the hypothesis that the eosinophil mediates damage to the respiratory epithelium and is the prime effector cell in the pathophysiology of asthma.