Five lines of evidence support the hypothesis that the eosinophil, possibly through its granule proteins, mediates bronchial hyperreactivity. First, bronchial hyperreactivity and blood eosinophilia are associated in patients with asthma. Second, bronchial hyperreactivity is associated with the number of eosinophils and the levels of eosinophil granule MBP in BAL fluids. Third, direct instillation of MBP into the lungs of monkeys caused bronchospasm and increased reactivity to methacholine. Fourth, direct application of MBP to respiratory epithelium caused increased smooth muscle reactivity to acetylcholine, suggesting that MBP stimulates respiratory epithelium to produce factors active on smooth muscle. Fifth, MBP causes allosteric inhibition of lung M2 muscarinic receptors.