Methacholine airway responsiveness has been observed to be related to prechallenge level of pulmonary function; however, normal ranges of responsiveness for specific levels of lung function have not been reported. We examined methacholine airway responsiveness in relation to level of prechallenge pulmonary function in a sample of 547 middle-aged and elderly men who denied any history of respiratory illness or symptoms and who had normal levels of prechallenge FEV1 and FEV1/FVC ratio. The cumulative dose of methacholine provoking a 20 percent decline in FEV1 (PD20FEV1) was positively correlated with prechallenge FEV1 percent predicted (Spearman correlation r = 0.35, p < 0.0001). The fifth percentile of PD20FEV1, chosen as an estimate of the lower limit of the normal range, varied with the level of prechallenge FEV1. When applied to a larger sample of 838 men with normal pulmonary function, the use of FEV1-specific cut-off values to separate "normal" from "abnormal" PD20FEV1 did not improve the sensitivity or specificity of methacholine challenge as a test for questionnaire-reported asthma or wheezing. These data provide lower limits of normal PD20FEV1 which are specific for a subject's prechallenge FEV1; however, these FEV1-specific lower limits of normal PD20FEV1 provided no greater sensitivity and specificity for detecting asthma and wheezing than did a single lower limit of normal PD20FEV1 for all subjects.