Airway responsiveness of infants is evaluated during sleep and the infants inhale the bronchial challenge agent via the nasal airway. Since stimulation of the nasal airway may produce bronchoconstriction, it is unclear whether the observed response in the infants results from deposition of the aerosol in the lower airways or from stimulation of nasal receptors. Therefore, in 6 healthy infants we compared the changes in partial expiratory flow-volume (PEFV) curves produced by aerosol inhalation of methacholine and the changes produced by instillation of equivalent doses of methacholine liquid into the nares. Following aerosol, the peak expiratory flow and the flow at functional residual capacity decreased, PEFV curves became concave in shape, and the oxygen saturation (SaO2) decreased. The highest methacholine concentration inhaled by any infant was 1.25 mg/mL. In contrast to aerosol delivery, a maximal methacholine concentration of 10.0 mg/mL was instilled into the nares of all 6 infants without any change in maximal flow at functional respiratory capacity (VmaxFRC) or SaO2. There was a significant decrease in peak flow and flattening of the PEFV curves at higher lung volumes; however, the PEFV curve remained convex in shape at the lower lung volumes. The changes in the PEFV curve following nasal instillation of methacholine are consistent with an increase in nasal resistance and no change in the lower airways. We conclude that the bronchoconstriction observed following inhaled methacholine does not result from stimulation of nasal receptors.