In an effort to explain the large variation of airway reactivity to histamine in human subjects in vivo, we have examined the relationship between histamine responses in vivo and isoproterenol in vitro. The bronchial reactivity in patients with lung carcinoma was assessed prior to surgery by measuring the provocative concentration of histamine that resulted in a 20 or a 40% reduction in either forced expiratory volume in one second or specific airway conductance (SGaw). We also determined the pD₂ value (-Log EC₅₀ molar) to histamine and isoproterenol in isolated bronchial muscle preparations from these subjects. A wide range of histamine responsiveness was observed in vivo for the 17 patients (PC₄₀ SGaw: 1.3 to greater than 64 mg/ml of histamine). There was no correlation between this latter parameter and the bronchial histamine sensitivity in vitro. However, isolated bronchial muscle preparations from asthmatic subjects were less sensitive to isoproterenol than were those preparations from nonasthmatic subjects.