Plateaus on the inhalation concentration-response curve have been described in normal subjects and patients with mild asthma. To determine the prevalence of plateaus on inhalation concentration-response curves, and the position of the curves in normal subjects, we measured complete dose-response curves for methacholine (1 mg/ml to 256 mg/ml) in 73 nonatopic, nonsmoking, nonasthmatic normal subjects between the ages of 20 and 76 yr. Measurements included FEV1, maximal expiratory flow at 50% and 30% of vital capacity on partial and complete forced expiratory flow-volume curves (Vmax50p, Vmax50c, Vmax30p, Vmax30c) and pulmonary resistance (RL). Plateau responses, EC50 values and slopes were measured. Plateaus were present in 25, 27, 24, 34, 35, and 16 subjects for FEV1, Vmax50c, Vmax30c, Vmax50p, Vmax30p, and RL, respectively. In those who achieved a plateau, the mean maximal decrease in FEV1 (+/- SD) was 21 +/- 8%, in Vmax50c it was 46 +/- 16%, in Vmax50p it was 67 +/- 12%, in Vmax30c it was 58 +/- 21%, and in Vmax30p it was 75 +/- 15%, and the increase in RL was 213 +/- 89%. In summary, the results of this study showed that easily identifiable plateaus develop on the inhalation concentration-response curves of approximately 40% of normal subjects after only moderate decreases in maximum flow and increases in RL. Maximal response at the plateau was greater on partial flow-volume curves and at lower lung volumes (30% versus 50% of VC). Comparison of these data with data from patients at risk for airway hyperresponsiveness will allow definition of the mechanisms leading to airway hyperresponsiveness.