The characteristics of bronchial hyperresponsiveness (BHR) were studied in 18 smokers with mild chronic air-flow limitation (CAL) by measuring responsiveness to inhaled histamine, methacholine (high dose), methoxamine (an alpha-adrenergic agonist), and histamine after ipratropium bromide. The response of the smokers to histamine was reproducible and in the same range as that found in asthmatics. The smokers were significantly less responsive to methacholine than to equimolar doses of histamine (p less than 0.001). The dose-response curves to methacholine reached a plateau or maximal effect after a 30 to 50% fall in FEV1 in 14 of the 16 smokers challenged. Only 1 of the subjects responded to alpha-adrenoreceptor stimulation, and pretreatment with ipratropium bromide had no effect on the histamine dose-response curve. By comparing these results with previously published data from similar studies performed on asthmatic subjects, it is concluded that BHR in smokers with CAL has characteristics different from those that occur in subjects with asthma.