Lung volume has been shown to be a major determinant of the bronchoconstrictor response to inhaled methacholine (MCh). Because a change in body posture from sitting to supine is associated with a reduction in lung volume, we hypothesized that airway responsiveness to inhaled MCh should be affected by body posture. Responsiveness to MCh was assessed in both sitting and supine postures on separate days in 10 subjects aged 24 to 42 yr. Subjects inhaled aerosols of saline and MCh in progressively doubling concentration (0.125 to 256 mg/ml). Responses were assessed by measuring partial and complete forced expiratory flow-volume curves (PEFV and MEFV, respectively). As indices of airway responsiveness, we took the MCh concentration ([MCh]) at which the FEV1 fell by 10% relative to postsaline (PC10), the maximal percentage fall in FEV1 (MR), the [MCh] at which FEV1 reached 50% of MR (EC50), and the [MCh] at which the flow at 20% vital capacity on PEFV curves fell by 20% relative to postsaline (FP20). Responsiveness to MCh was increased in the supine compared with the sitting posture. In the sitting posture, the geometric mean values of MR, PC10, and FP20 were 16.3%, 16.3 mg/ml, and 2.0 mg/ml; supine they were 29.9% (p less than 0.009), 3.0 mg/ml (p less than 0.02), and 0.6 mg/ml (NS), respectively. EC50 did not change with posture. These results are consistent with the notion that airway responsiveness is influenced by airway-parenchymal interdependence and indicate that the results of bronchial provocation testing in the supine posture cannot be directly compared with those in the upright posture.