The provocative concentrations of inhaled methacholine that cause 6% (PC6) and 20% (PC20) falls in forced expiratory volume in one second (FEV1) were assessed in a population of 100 nonsmoking persons, equally distributed for sex, who ranged uniformly from 20 to 60 yr of age. These subjects had no respiratory symptoms, rhinitis, atopic history, or familial history of asthma. Single twofold dilutions of methacholine from 2 to 128 mg/ml were used; 81 and 34 subjects, respectively, showed PC6 and PC20 values less than 128 mg/ml. Eight subjects had PC20 values less than 16 mg/ml. In these subjects, the test had a good reproducibility (r = 0.92) when we repeated it, and serial measurements of peak expiratory flow rates did not suggest asthma. The fact that PC6 was related, although loosely, to baseline FEV, FEV/FVC, and forced expiratory flow during the middle half of the FVC (FEF) and that 4 of the 8 subjects with PC20 values less than 16 mg/ml had lower values of FEF might suggest that responsiveness to methacholine is partially linked with baseline airway caliber.