Regional blood flow in the lung is known to be influenced by the alveolar PCO2 and alveolar PO2. For the healthy lung, the extent to which this influence is of functional importance in limiting heterogeneity in alveolar gas composition by matching regional perfusion (q) to regional ventilation (v) remains unclear. To address this issue, the efficiency of regulation (E) was defined as the percent correction to an initial perturbation in regional alveolar gas composition generated by the pulmonary vascular response to the disturbance. This study develops the theory to calculate E from global measurements of vascular reactivity to CO2 and O2 in human volunteers. For O2, these data were available from the literature. For CO2, an experimental component of the present study used Doppler echocardiography to evaluate the magnitude of the global vascular response to hypercapnia and hypocapnia in 12 volunteers over a timescale of approximately 0.5 h. The results suggest a value for E of approximately 60% over a wide range of values for v-to-q ratio (approximately 0.1-10) encompassing those found in normal lung. At low v/q (<0.65), the vascular response to O2 forms the dominant mechanism; however, at higher v/q (>0.65), the response to CO2 dominates. The values for E suggest that the pulmonary vascular responses to both CO2 and O2 play a significant role in ventilation-perfusion matching in the healthy human lung.