Arterial oxygen saturation (SaO2) is usually measured during inhalation challenges in infants as desaturation has been demonstrated with provoked bronchoconstriction. We wished to examine whether measurement of SaO2 would provide a simple noninvasive indicator of respiratory function (RF) changes occurring during inhalation challenge in infants. Histamine inhalation challenges were performed longitudinally in 22 normal healthy infants at 4 and 26 weeks of age. RF was measured by calculating maximum forced expiratory flow at functional residual capacity (VmaxFRC) using the rapid thoracic compression technique. Airway responsiveness was assessed using histamine; the provoking concentration (PC) was that which caused a fall in VmaxFRC of at least 40% from baseline. The provocative concentration for an exact fall of 40% in VmaxFRC (PC40) from baseline was derived by linear interpolation. SaO2 was continuously monitored by pulse oximetry. One month old infants had higher SaO2 levels throughout the inhalation challenge in comparison to their SaO2 levels at 6 months of age. Significant falls in SaO2 were observed at the PC at both ages. However, at the age of 26 weeks the infants had greater median falls in SaO2 [PC, 4.5% (95%CI: 3.0, 7.0)] compared to the response at age 4 weeks [3.0% (95%CI: 1.0, 4.0) (P < 0.01)]. Median falls in VmaxFRC at the PC were not different between the ages. These results indicate an age-dependent discordance between airway and SaO2 response in healthy infants during histamine-induced bronchoconstriction.