The study was designed to compare in vivo responses to histamine in 14 patients prior to thoracotomy with in vitro responses to histamine of both parenchymal and bronchial tissue. Although a wide range of responsiveness occurred in vivo, as measured by the histamine inhalation test, the variation in the in vitro dose-response curves was negligible. There was no correlation between the dose of histamine that resulted in a 20% reduction in forced expiratory volume in one second and the concentration of histamine producing 50% of the maximal response in vitro. These findings raise the possibility that airway hyperresponsiveness may not result from an intrinsic abnormality of airway smooth muscle.