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We investigated 654 subjects of a small Lombardy (Italy) town between 15 and 64 years of age who were representative of the general population. By clinical examination, the sample included 535 normal subjects (164 normal smokers, 341 normal nonsmokers, 30 normal subjects with acute upper respiratory illness within 30 days before the challenge), 50 with chronic bronchitis, 26 with asthma, and 43 with allergic rhinitis. Subjects whose FEV1was 75 percent or more than the predicted value (654) underwent methacholine bronchial challenge by means of 1 percent metered-dose solution. The test result was considered positive at a drop of more than 15 percent in FEV1(compared with buffer). Normal smokers and all of the groups with disease had a significantly different distribution of reactivity compared with normal nonsmokers. The difference between asthmatic and these “normal” subjects was highly significant; nevertheless, a clear cut-off between the two groups does not appear to exist.