We assessed the relationship between bronchial hyperresponsiveness (BHR) and the onset of wheezing 5 years later, by epidemiological analysis of 194 working men without asthma or wheezing at the first examination. In 1985/ 1986 and 1990/1991, subjects answered a British Medical Research Council questionnaire and performed lung function measurements and methacholine challenge tests (total dose 6 mg). BHR was measured in three ways: (1) FEV1 fall ≥ 20% (PD20+); (2) the two-point response slope expressed as percentage decline of FEV1/dose, and (3) a four-parameter model: FEV1 at dose (d)/ prechallenge FEV1 = ONE-k(d-δ)α+, where ‘k’ is the slope of the relative variation of FEV1 with the dose, ‘δ’ the threshold dose, and ‘α’ a shape factor. In the 13 new wheezers, the mean values of the two-point slope and of k were significantly increased, and the proportion of reactors was almost threefold (the latter was not statistically significant). Among nonsmokers, δ was significantly lower in new wheezers than in the others, whereas the slope and k had similar mean values. Among smokers, new wheezers had increased mean values for the slope and k, and an increased proportion of reactors, whereas δ was not decreased. Thus, BHR was a significant predictor of wheezing, independent of the method of analysis. Moreover, the model distinguished between two components of bronchial response: wheezing was predicted by sensitivity (δ) in nonsmokers, and by reactivity (k) in smokers.