Lesions in small airways may cause increased central deposition of inhaled aerosol. This may enhance airway constriction following methacholine (MCh) challenge. Heterozygous alpha 1-antitrypsin deficiency (PiMZ) and smoking may both act on the lung parenchyma and may also influence small airways. We, therefore, have related bronchial reactivity to MCh to the function of the small airways and to smoking habits in 31 normal (PiM) male subjects aged 48-50 years and 34 PiMZ male subjects, all from a population study. A total of 23 subjects with increased bronchial reactivity was found. The number of reacting smokers (14/23) was significantly higher than that of the reacting ex-smokers (7/23) (p less than 0.05) and nonsmokers (2/19) (p less than 0.05). The smokers who had increased reactivity to MCh challenge had significantly higher closing capacity %, RV/TLC %, and volume of trapped gas % than the smokers who did not have increased reactivity. This difference was not seen with regard to closing volume %, slope index, delta N2 %/1, or washout volume. There was no significant difference between the PiM and the PiMZ subjects with regard to any of the lung function variables or the response to the MCh challenge. It is concluded that there may be a correlation between dysfunction of the small airways and increased bronchial reactivity.